Search

The detection of carbohydrate antigen 19-9 (CA199), a critical biomarker for pancreatic, colorectal, and gastric cancers, is essential for early diagnosis and disease monitoring. Traditional antibody-based assays for CA199 detection are limited by high costs, time-consuming procedures, and susceptibility to nonspecific interference. This study presents an electrochemical biosensor based on a multifunctional poly(EDOT-PyBA- co -EDOT-PEG) copolymer designed to overcome these limitations. The biosensor integrates pyridylboronic acid (PyBA) moieties for specific recognition of sialic acid residues and poly(ethylene glycol) (PEG) chains for antifouling properties within a conductive PEDOT framework. By eliminating antibody dependency, the biosensor reduces costs, enhances stability, and simplifies the diagnostic process. Surface characterization confirmed the successful incorporation of PyBA and PEG units, while electrochemical impedance spectroscopy enabled sensitive detection of CA199 with a limit of detection of 0.05 U·mL -1 and a linear response range from 0.05 to 40 U·mL -1 . Recovery tests in spiked human serum samples demonstrated excellent accuracy (97-109% recovery), validating the biosensor's reliability in complex biological matrices. The rationally designed copolymer provides both high sensitivity and specificity while maintaining resistance to biofouling in serum samples. This work establishes a scalable, cost-effective platform for glycoprotein biomarker detection, advancing the field of clinical diagnostics and cancer monitoring.

Background: Neoadjuvant chemotherapy (NAC) can provide improved survival outcomes in pancreatic ductal adenocarcinoma (PDAC) patients who respond to treatment, but currently available biomarkers cannot reliably predict NAC response. This study aimed to determine the potential of a previously identified diagnostic and prognostic biomarker panel (i.e. Ca-125, S100A2, S100A4, Mesothelin and Ca19-9) for the monitoring of NAC-response in PDAC patients., Methods: This single-centre, retrospective study, utilised serum from NAC treated PDAC patients to determine the levels of biomarkers by Enzyme-Linked Immunosorbent Assay (ELISA). The percentage of the tumour bed occupied by viable carcinoma (PVC) was used to divide patients into good (PVC < 50%) and poor (PVC ≥ 50%) NAC-responders. Statistical analysis was performed to measure the ability of individual biomarkers and a biomarker panel in NAC treatment response and patient survival., Results: Serum specimens from a total of 108 PDAC patients were assessed. Ca-125, Ca19-9 and S100A2 showed a significant positive correlation with PVC. Ca-125 demonstrated a superior ability to monitor NAC treatment response (Area under receiver operating curve (AUC): .6954) compared to the more widely used clinical biomarker, Ca19-9 (AUC: .6291). A panel of Ca-125 and Ca19-9 showed good ability to monitor NAC response in PDAC patients (AUC: .7349). Patients with high levels of both Ca-125 and Ca19-9 were shown to have the poorest overall survival (median overall survival: 17 vs. 30 months)., Conclusion: A serum biomarker panel of Ca-125 and Ca19-9 could be used for effective clinical management of PDAC patients undergoing NAC treatment., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Objective: To investigate the relationship between serum tumor markers and the severity of silicosis. Methods: In April 2024, A cluster sampling was conducted on the pulmonary rehabilitation centers in Jiangsu Province. A retrospective analysis was carried out on 629 patients who received follow-up physical examinations for pneumoconiosis from April to November 2023 at the selected rehabilitation centers. 281 healthy volunteers who underwent occupational health examinations at our institution were selected as the blank control group, and 384 dust exposed workers from a coal mining enterprise were selected as the dust exposed control group. Detect the levels of peripheral bloodtumor markers carcinoembryonic antigen CEA, carbohydrate antigen CA199, and neuron-specific enolase NSE in specimens. Measure the patient's forced vital capacity (FVC), forced expiratory volume in one second (FEV(1)), and lactate acid dehydrogenase (LDH) levels in the blood. The Jonckheere-Terpstra test, a non-parametric test for ordered independent samples, was used to compare the expression levels of tumor markers among multiple groups. Spearman's rank correlation analysis was adopted to explore the correlations between serum tumor markers and the staging of pneumoconiosis as well as lung function parameters. Results: Among the 629 patients with pneumoconiosis, 454 were in stage Ⅰ, 150 were in stage Ⅱ, 25 were in stage Ⅲ. There were significant differences in serum CEA, CA199 and NSE levels among patients with different periods of pneumoconiosis, blank control group and dust-exposed control group ( P <0.001). Serum CEA, CA199 and NSE levels were positively correlated with pneumoconiosis stage ( P <0.05). There is a negative correlation between serum CA199 levels and FEV(1)% in patients with pneumoconiosis ( r =-0.082, P <0.05). The serum CA199 level was positively correlated with LDH in patients with pneumoconiosis ( r =0.108, P <0.05) .The serum NSE level of pneumoconiosis patients was negatively correlated with FVC% ( r =-0.079, P <0.05) .There is a positive correlation between serum NSE levels and LDH in patients with pneumoconiosis ( r =0.435, P <0.05) . Conclusion: The serum CA199 and NSE of pneumoconiosis patients are directly related to the severity and stage of the disease, which have practical significance in judging the treatment effect of pneumoconiosis patients and monitoring the development of the disease.

Backgrounds: To discern the potential of KL-6 and CA-153 as diagnostic tools for interstitial lung disease (ILD), understand their relationship with GAP (Gender, Age, and Physiology) stage, and analyze their predictive capacities alongside CT features. This research aims to enhance ILD detection and management in autoimmune patients, emphasizing the diagnostic utility of these biomarkers., Methods: From Mar 2017 to Mar 2024, 398 patients from Taichung Veterans General Hospital's Division of Allergy, Immunology, and Rheumatology with autoimmune diseases were prospectively enrolled. ILD diagnoses were confirmed using High-Resolution Computed Tomography (HRCT) or lung biopsy and characterized by radiologists. GAP scores were calculated for IPF prognosis. 583 serum samples were collected and tested for KL-6, CA-153, CA-199, and CA-125 using specific assays. Statistical analyses compared patients, assessed variables, determined missingness, and predicted ILD, with tools like ROC analysis and logistic regressions. Analyses were performed with IBM SPSS and MedCalc., Results: ILD patients were older, predominantly male, and had more smokers compared to non-ILD. Both KL-6 and CA-153 were higher in ILD and showed a significant, but non-interchangeable correlation. Age, BMI, smoking, and biomarker levels influenced ILD odds, with KL-6 and CA-153 being the strongest predictors. HRCT imaging highlighted these markers' roles, especially in detecting specific features. Both markers also strongly associated with GAP stages. Stratified analyses emphasized KL-6's significance in predicting ILD across both AD and non-AD groups. Complete data sensitivity analysis reinforced KL-6 and CA-153 as key ILD predictors., Conclusions: This research emphasizes CA-153 as a feasible, cost-effective alternative to KL-6 in diagnosing and monitoring ILD. Both CA-153 and KL-6 levels were notably elevated in ILD patients, displaying a strong correlation, especially at CA-153 levels of ≤100 U/ml. They both also have significant associations with CT characteristics and GAP stages. The study reinforces the potential of CA-153, particularly in settings where KL-6 testing might be inaccessible or expensive., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Colorectal cancer is one of the most common malignant tumors in the world, and about 50% of its advanced patients will have liver metastasis. Preoperative assessment of the risk of liver metastasis in patients with colorectal cancer is of great significance for making individualized treatment plans. Traditional imaging examinations and tumor markers have some limitations in predicting the risk of liver metastasis. Therefore, it is of great clinical value to explore more sensitive and specific predictive indicators for improving early detection and treatment effect. In recent years, circulating tumor cells (CTCs), as a new biomarker, have attracted much attention because of their close relationship with tumor metastasis and prognosis. The purpose of this study is to collect and analyze the data of colorectal cancer patients treated in our hospital, so as to determine the predictive value of circulating tumor cells before operation and related hematological indexes for liver metastasis after radical resection of colorectal cancer, and to establish the corresponding prediction model to provide gastrointestinal surgeons with more accurate identification of high-risk patients and guidance for treatment. A total of 88 patients were included in this study, and 26 of whom developed liver metastasis after colorectal cancer surgery. The possible related factors are included in the single factor logistic regression, and the results are obtained after analysis. Body mass index, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9, tumor marker CA72-4 (CA72-4), cytokeratin-7 (CK-7), CTC count, and neutrophil-to-lymphocyte ratio (P < .2) are risk factors for liver metastasis after radical resection of colorectal cancer. Furthermore, the data obtained were included in multivariate regression analysis, and CEA, CA72-4, CK-7, and CTC counts were independent risk factors for liver metastasis after radical resection of colorectal cancer (P < .05). This study confirmed that CEA, CA72-4, CK-7, and CTC counts are independent risk factors for liver metastasis after radical resection of colorectal cancer. In addition, the prediction model of this study can help gastrointestinal surgeons accurately identify patients who are prone to liver metastasis after colorectal cancer surgery., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Colorectal cancer has a high incidence and mortality rate due to a low rate of early diagnosis. Therefore, efficient diagnostic methods are urgently needed., Purpose: This study assesses the diagnostic effectiveness of Carbohydrate Antigen 19-9 (CA19-9), Carcinoembryonic Antigen (CEA), Alpha-fetoprotein (AFP), and Cancer Antigen 125 (CA125) serum tumor markers for colorectal cancer (CRC) and investigates a machine learning-based diagnostic model incorporating these markers with blood biochemical indices for improved CRC detection., Method: Between January 2019 and December 2021, data from 800 CRC patients and 697 controls were collected; 52 patients and 63 controls attending the same hospital in 2022 were collected as an external validation set. Markers' effectiveness was analyzed individually and collectively, using metrics like ROC curve AUC and F1 score. Variables chosen through backward regression, including demographics and blood tests, were tested on six machine learning models using these metrics., Result: In the case group, the levels of CEA, CA199, and CA125 were found to be higher than those in the control group. Combining these with a fourth serum marker significantly improved predictive efficacy over using any single marker alone, achieving an Area Under the Curve (AUC) value of 0.801. Using stepwise regression (backward), 17 variables were meticulously selected for evaluation in six machine learning models. Among these models, the Gradient Boosting Machine (GBM) emerged as the top performer in the training set, test set, and external validation set, boasting an AUC value of over 0.9, indicating its superior predictive power., Conclusion: Machine learning models integrating tumor markers and blood indices offer superior CRC diagnostic accuracy, potentially enhancing clinical practice., Competing Interests: Declarations. Conflict of interest: The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Ethical approval: The study was approved by the Ethics Committee of the First Hospital of Dalian Medical University. Informed consent: For this type of study, formal consent is not required., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Cancer biomarkers have been facing some issues such as poor accuracy and low sensitivity in the early diagnosis of tumors. Utilizing biotin-labelled peptide as a mass tag (MT), this work proposes a high-throughput biosensing strategy for matrix-assisted laser desorption/ionization-time of flight mass spectrometric (MALDI-TOF-MS) immunoassay of multiple lung cancer biomarkers. Due to little required dosage, satisfied stability, high sensitivity and accuracy, this method can achieve off-site centralized signal detection after on-site sample incubation. The proposed approach has been successfully applied for the detection of carcinoembryonic antigen (CEA), carbohydrate antigen199 (CA199), carbohydrate antigen 125 (CA125) and cytokeratin-19-fragment (CY211) in serum samples from various stages of non-small cell lung cancer. Based on the analysis of multiple parameters and pathological results, significant differences in biomarkers are found in serum samples of lung cancer patients at different stages. More importantly, the analysis of multiple tumor biomarkers can improve the accuracy and sensitivity of early diagnosis. Therefore, the multiple immunoassay based on MALDI-TOF MS exhibits exceptional performance in terms of high throughput, little sample dosage, stability and sensitivity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Here, a label-free immunosensor was conducted using rGO/Collard-like Bi 2 S 3 @Au nanocomposite system to detect carbohydrate antigen 19-9 (CA19-9) as a diagnostic biomarker for Pancreatic cancer. The unique morphology of Collard-like Bi 2 S 3 increases its specific surface area, which allows it to immobilize more materials and biomolecules on its surface. To realize the covalent bonding of bismuth-based materials with biomolecules, bismuth-based materials were functionalized by Au NPs. Besides, the superior electrochemical activity and large specific surface area of Bi 2 S 3 @Au improved the stability of the sensor, which made it an ideal candidate for regulating the sensing interface in this study. Meanwhile, reduced graphene oxide (rGO) with remarkable electrical conductivity to improve the current response of the sensing interface, thus broadening the linear range of the immunosensor. Based on the above materials, a label free electrochemical immunosensor was constructed for detecting CA19-9. Under optimal conditions, it displays good linear relationship within the range of 0.01 U mL -1 to 100 U mL -1 , the detection limit being 0.0012 U mL -1 . Additionally, the immunosensor prepared in this work is characterized by superior interference immunity, reproducibility and storage stability, and has yielded satisfactory recovery rate in testing the serum samples of patients., Competing Interests: Declaration of Competing interest I, Yarui An, declare that there are no conflicts of interest in relation to the manuscript titled "Collard-like Bi(2)S(3)@Au nanocomposites-based label free electro-chemical immunosensor for quantitative detection of CA19-9″ submitted to Tanlanta. I confirm that the results and interpretations reported in the manuscript are original and have not been plagiarized. I certify that I have read and understand the Talanta conflict of interest policy, and I understand that failure to disclose a conflict of interest may result in the manuscript being rejected or retracted. I also certify that I have disclosed any financial or non-financial relationships that may be interpreted as constituting a conflict of interest in relation to this manuscript. I understand that this information subject to peer review, and I am willing to provide further information or clarification if required. I confirm that I have no known conflicts of interest that would influence the results or interpretation of the data presented in this manuscript, and understand that failure to disclose a conflict of interest is unethical and may result in sanctions being imposed on me., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Sensitive detection of tumor biomarkers is of great significance for early cancer diagnosis, treatment evaluation, and recurrence monitoring. Development of convenient electrochemiluminescence (ECL) immunosensor using dissolved oxygen (O 2 ) as an endogenous co-reactant of luminol combined with efficient nanocatalysts to boost ECL signal in neutral media is highly desirable. Herein, sensitive detection of tumor biomarker using ECL of luminal-O 2 enhanced by confinement of nitrogen-doped graphene quantum dots (N-GQDs) and platinum nanoparticles (PtNPs) on nanochannel array was demonstrated. A high-density nanochannel array-modified electrode was achieved by rapidly growing an amino-functionalized. Vertically-ordered mesoporous silica film (NH 2 -VMSF) on the inexpensive and readily available indium tin oxide (ITO) electrode. Through simple electrodeposition, N-GQDs were confined and PtNPs were in-situ synthesized in nanochannels of NH 2 -VMSF. These confined nanocomposites catalyzed the electroreduction of O 2  at negative potentials to generate a large amount of reactive oxygen species (ROS) and facilitated luminol oxidation, enhancing the ECL signal of luminol by 25 times. Two immunosensors were fabricated after covalent immobilization of the recognition antibody of carbohydrate antigen 199 (CA199) or carbohydrate antigen 125 (CA125) on the outer surface of the NH 2 -VMSF and blocking of non-specific sites. When tumor biomarkers bind to the corresponding antibodies on the recognition interface, the formed immunocomplex hindered the diffusion of luminol to the underlying electrode, resulting in a decrease in the ECL signal and sensitive detection of tumor biomarker. The constructed CA199 immunosensor exhibited a linear detection range for CA199 from 0.5 mU mL -1  to 50 U mL -1 , with a detection limit (DL) of 0.03 mU mL -1 . For CA125 detection, linear detection ranged from 0.5 mU mL -1  to 500 U mL -1 , with a DL of 0.005 mU mL -1 . The fabricated immunosensors demonstrated good selectivity and high reproducibility. This study provides great potential for the development of efficient luminol ECL systems in neutral media and expands the biological application in sensitive detection of tumor biomarker., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A novel label-free electrochemical immunosensor for the ultrasensitive determination of cancer antigen (CA724) was developed using a novel composite of CoAl layered double hydroxides (CoAl-LDH) and carboxyl-functionalized multiwall carbon nanotubes (MWCNTs-COOH) as platform and ferrocenecarboxylic acid (Fc-COOH) as signal label. The MWCNTs-COOH/Fc-COOH@CoAl-LDH composite was prepared by a convenient and simple one-step ultrasonic method, and various characterization techniques consisting of scanning electron microscopy (SEM), transimission electronic microscopy (TEM), TEM-Mapping, fourier transform infrared (FT-IR), X-ray diffraction (XRD) and X-ray photoelectronic energy spectrum (XPS) were applied to study the size and morphological features. Due to its large specific surface area and multilayer structure, the CoAl-LDH can be post-doped to embed a large amount of signal probe to realize the amplification of the internal reference signal Fc. In addition, the higher conductivity of MWCNTs-COOH compensates for the deficiency of CoAl-LDH, which effectively strengthened the electron transfer efficiency of electrochemical signaling substances. The optimal experimental conditions were detected to be 2.5 mmol of Fc-COOH, 4.0 mg/mL of concentration, pH 6.0, incubation time of 40 min, and incubation temperature of 37 ℃. Under optimal conditions, the fabricated sensor exhibits linearity in a wide dynamic range covering the physiological concentration, from 0.001 to 100 U/mL and the limit of detection (LOD) was 0.03962 mU/mL, the calibration equation is stated as △I = 7.76363 log 10 C CA724  + 40.50351 (R 2  = 0.99674). The sensor is successfully detects trace levels of CA724 in human serum with excellent recovery rates ranging from 100.52 %-102.30 %, proving the synergy of MWCNTs-COOH/Fc-COOH@CoAl-LDH as a promising platform for electrochemical sensing for clinical detection of other disease markers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

This study explores the application of serum biomarkers in the diagnosis of adenomatous polyps and evaluates the effectiveness of different markers and their combined diagnosis in adenomatous polyp detection. Using receiver operating characteristic curve analysis, this study assessed the efficacy of serum biomarkers such as carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), alpha-fetoprotein (AFP), carbohydrate antigen 199 (CA199), and prothrombin time (PT) in diagnosing adenomatous polyps in 90 patients. The study also compared the diagnostic accuracy of individual tests versus combined diagnostic approaches and analyzed the impact of polyp size and number on the levels of these markers. Among the individual tests, CA125 showed relatively high diagnostic efficacy. However, combined diagnostic approaches, such as the combination of CEA and CA125, the trio of CEA, CA125, and AFP, and the quartet of CEA, CA125, AFP, and PT, significantly improved diagnostic sensitivity and specificity. Additionally, the study found that the size and number of adenomatous polyps significantly influenced the levels of CEA, CA125, CA199, and PT, with larger and more numerous polyps associated with higher marker levels. This study demonstrates that combined diagnostic strategies have significant advantages in diagnosing adenomatous polyps, providing more accurate and comprehensive diagnostic information. Furthermore, the impact of polyp size and number on serum biomarker levels suggests that these clinical factors should be considered in clinical assessments. These findings offer new perspectives and approaches for the diagnosis of adenomatous polyps., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Ovarian steroid cell tumor, not otherwise specified (SCT-NOS), is a rare subtype of sex cord-stromal tumor, characterized by hirsutism and virilization. There are, however, few tumor markers reported in the tumor. The following is a case report. Six years ago, the patient underwent a left adnexectomy after being diagnosed with a yolk sac tumor. Her serum CA72-4 levels were significantly elevated when she was diagnosed with SCT-NOS. She suffered from hirsutism and oligomenorrhea with long menstrual cycles. SCT-NOS was confirmed by her histopathological examination. When the tumor was diagnosed, serum CA72-4 levels were elevated. Following tumor resection, serum CA72-4 levels returned to the average reference interval. Whole-exome sequencing (WES) was utilized to identify ten mutations in MKI67, TICAM1, CHD3, ARID5B, ERBB4, POLD1, FZR1, MTCP1, TBX3, and CLTC genes.

Background: Gastric cancer (GC) is a highly prevalent gastrointestinal tract tumor. Several trials have demonstrated that the location of GC can affect patient prognosis. However, the factors determining tumor location remain unclear., Aim: To investigate the tumor location of patients, we went on to study the influencing factors that lead to changes in the location of GC., Methods: A retrospective evaluation was carried out on 3287 patients who underwent gastrectomy for GC in Zhejiang Cancer Hospital. The patients were followed up post-diagnosis and post-gastrectomy. The clinicopathological variables and overall survival of the patients were recorded. By analyzing the location of GC, the tumor location was divided into four categories: "Upper", "middle", "lower", and "total". Statistical software was utilized to analyze the relationship of each variable with the location of GC., Results: A total of 3287 patients were included in this study. The clinicopathological indices of gender, age, serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen (CA19-9) and CA72-4 levels, were significantly associated with tumor location in patients with GC. In addition, there was a strong correlation between GC location and the prognosis of postoperative patients. Specifically, patients with "lower" and "middle" GC demonstrated a better prognosis than those with tumors in other categories., Conclusion: The five clinicopathological indices of gender, age, CEA, CA19-9 and CA72-4 levels exhibit varying degrees of influence on the tumor location. The tumor location correlates with patient prognosis following surgery., Competing Interests: Conflict-of-interest statement: Author(s) certify that there is no conflict of interest related to the manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: CA 72-4 is a tumor associated antigen which shows significantly increased serum levels in gastric cancer. It is the most commonly used serum tumor marker for diagnosing symptomatic gastric cancer and monitoring gastric cancer treatment., Methods: We report the case of a gout patient with abnormal elevation of serum CA 72-4 caused by taking colchicine., Results: The patient's painless gastroscopy and other examinations showed no obvious abnormalities, and no detection interference was detected. After discontinuing treatment with colchicine, CA 72-4 level of the patient returned to normal. Therefore, the abnormal increase of CA 72-4 is believed to be caused by colchicine., Conclusions: When gout patients receive colchicine treatment, it may lead to an abnormal increase in CA 72-4 results. Laboratory staff should consider the existence of such interference and promptly remind clinical doctors to avoid unnecessary examination and treatment of patients.

A blood test that enables surveillance for early-stage pancreatic ductal adenocarcinoma (PDAC) is an urgent need. Independent laboratories have reported PDAC biomarkers that could improve biomarker performance over CA19-9 alone, but the performance of the previously reported biomarkers in combination is not known. Therefore, we conducted a coordinated case/control study across multiple laboratories using common sets of blinded training and validation samples (132 and 295 plasma samples, respectively) from PDAC patients and non-PDAC control subjects representing conditions under which surveillance occurs. We analyzed the training set to identify candidate biomarker combination panels using biomarkers across laboratories, and we applied the fixed panels to the validation set. The panels identified in the training set, CA19-9 with CA199.STRA, LRG1, TIMP-1, TGM2, THSP2, ANG, and MUC16.STRA, achieved consistent performance in the validation set. The panel of CA19-9 with the glycan biomarker CA199.STRA improved sensitivity from 0.44 with 0.98 specificity for CA19-9 alone to 0.71 with 0.98 specificity (p < 0.001, 1000-fold bootstrap). Similarly, CA19-9 combined with the protein biomarker LRG1 and CA199.STRA improved specificity from 0.16 with 0.94 sensitivity for CA19-9 to 0.65 with 0.89 sensitivity (p < 0.001, 1000-fold bootstrap). We further validated significantly improved performance using biomarker panels that did not include CA19-9. This study establishes the effectiveness of a coordinated study of previously discovered biomarkers and identified panels of those biomarkers that significantly increased the sensitivity and specificity of early-stage PDAC detection in a rigorous validation trial., Competing Interests: Declaration of competing interest AM is a consultant for Tezcat Biotechnologies and is a co-inventor on a patent that has been licensed from Johns Hopkins University by Thrive Earlier Detection (an Exact Sciences company). RB received research funding from Immunovia and Freenome and serves as on the advisory board for Immunovia. The authors declare no other reported potential conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Gastric cancer (GC) is a highly heterogeneous and aggressive malignant tumor that seriously affects the life safety of people all over the world. Its early manifestations are subtle. The present study aimed to investigate the clinical significance of serum lipid profiles, insulin resistance markers including the triglyceride-glucose (TyG) index and the atherosclerotic index (AI), in GC patients. A retrospective analysis encompassed 215 GC patients and 827 healthy individuals. The study results show that the total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein levels, and the TyG index of GC patients were significantly lower than those of the control group before and after propensity score matching analysis. In the GC group, the levels of CEA, CA199, CA125, and CA724 tumor markers were higher than those in the healthy control group. Patients in advanced stages exhibited lower serum levels of serum lipids and TyG index compared to those in early stages. ROC analysis revealed that the TyG index, CA125, and CA199 combination yielded the highest positive prediction rate for GC at 98.6%. TyG index is significantly associated with the risk of adverse reactions after chemotherapy (OR = 1.104, 95% CI 1.028-1.186, P < 0.01). Multiple tumor markers and the TyG index combined detection showed correlations with five adverse reactions caused by chemotherapy (r < 0.6, P < 0.05). Preoperative lipid profiles in the serum show a strong correlation with patients diagnosed with GC. Evaluating a combination of various serum lipids and cancer markers significantly improves diagnostic precision for GC and the ability to predict chemotherapy side effects., (© 2024. The Author(s).)

Objectives: The early imaging features of spinal tumors and spinal infections are similar, and the lack of specific early diagnostic indicators can lead to misdiagnosis or missed diagnosis. Although serum tumor markers have been widely used in early cancer screening, spinal tumors are mostly metastatic, lacking specific markers, and some patients with spinal tumors may even test negative for tumor markers. Therefore, the role of tumor markers in the early differential diagnosis of spinal tumors remains unclear. This study aims to investigate the value of tumor markers in the early differential diagnosis of spinal tumors and spinal infection., Methods: We retrospectively analyzed the clinical data of 221 patients with spinal bone destruction admitted to Xiangya Hospital of Central South University between April 2017 and October 2022. Peripheral blood levels of 10 tumor markers were measured upon admission, including carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), neuron-specific enolase (NSE), cytokeratin 19 fragment antigen 21-1 (cyfra21-1), carbohydrate antigen 199 (CA199), carbohydrate antigen 125 (CA125), carbohydrate antigen 72-4 (CA72-4), pepsinogen I (PGI), pepsinogen II (PGII), and the PGI/PGII ratio (PGR). Univariate Logistic analysis was used to screen relevant variables, and the correlation between tumor markers was analyzed. Multivariate Logistic regression was then employed to identify risk and protective factors. The optimal cut-off values were calculated using the receiver operating characteristic (ROC) curve and Youden index, and a differential diagnosis model for early spinal tumors and spinal infections was constructed based on the selected indicators. Diagnostic performance was then evaluated., Results: According to the pathological diagnosis, 91 patients had spinal tumors, and 130 patients had spinal infections. The levels of CEA, AFP, NSE, cyfra21-1, CA199, and CA72-4 were higher in the spinal tumor group than those in the spinal infection group, while PGR was lower, with statistically significant differences (all P <0.05). Univariate Logistic analysis showed significant differences in CEA, AFP, NSE, cyfra21-1, CA199, CA125, CA72-4, and PGR (all P <0.05). Correlation analysis indicated a strong positive correlation between CEA and cyfra21-1, CA199, and CA125, as well as a strong negative correlation of PGII with PGI and PGR. Multivariate Logistic analysis identified AFP and cyfra21-1 as risk factors ( P <0.01) and PGR as a protective factor ( P <0.05). When the standard cut-off values (AFP<20 ng/mL, cyfra21-1< 3.3 ng/mL, and PGR>3) were applied, AFP had a sensitivity of 3.3% and accuracy of 60.2%, cyfra21-1 had a sensitivity of 20.9% and accuracy of 66.1%, and PGR had a sensitivity of 2.2% and accuracy of 59.3%. The AUC of the early spinal tumor diagnosis model was 0.623. Using the optimal cut-off values (AFP<1.625 ng/mL, cyfra21-1<1.175 ng/mL, and PGR>11.05) from the ROC curve, AFP had a sensitivity of 69.2% and accuracy of 64.7%, cyfra21-1 had a sensitivity of 68.1% and accuracy of 70.1%, and PGR had a sensitivity of 62.6% and accuracy of 57.5%, with the model's AUC at 0.772., Conclusions: A comparative analysis of 10 serum tumor markers reveals that AFP, cyfra21-1, and PGR are significantly associated with spinal tumors. The diagnostic model constructed based on these 3 markers shows promising predictive performance and may be helpful to the differentiation for the early clinical diagnosis of spinal tumors and spinal infection.

Objectives: Gastric-type endocervical adenocarcinoma (GAS) is a special type of cervical adenocarcinoma that is not associated with high-risk human papilloma virus (HPV) infection, making early diagnosis challenging. This study aims to investigate the clinical characteristics, diagnosis, treatment, and prognosis of non-HPV infection-associated GAS, summarize relevant experiences, and improve the ability to recognize early lesions., Methods: A total of 21 patients with GAS treated at the Department of Gynecology, Third Xiangya Hospital of Central South University, from April 2016 to February 2023, were included. Clinical data, including age, clinical manifestations, HPV/thin-prep cytology test (TCT) results, tumor markers, imaging examinations, diagnostic methods, Federation International of Gynecology and Obstetrics (FIGO) (2018) staging, pathological results, immunohistochemistry findings, treatment, and follow-up outcomes were collected and analyzed. Kaplan-Meier method was used to calculate survival rates, log-rank test was used to calculate survival rates, log-rank test was used to compare survival differences, and Cox regression method was used to analyze prognostic factors., Results: The patients' ages ranged from 18 to 67 years [(48.4±12.0) years]. The most common initial symptom was noticeable vaginal discharge in 13 cases, followed by purulent vaginal discharge in 1 case, postmenopausal vaginal bleeding in 3 cases, bleeding during intercourse in 2 cases, prolonged menstruation in 1 case, and lower abdominal distension in 1 case. Except for 2 patients without sexual experience, the remaining patients underwent TCT and HPV testing, with 17 HPV-negative cases and 2 HPV-positive cases (1 for type 16 and 1 unclassified); TCT results were negative in 13 cases, with 2 cases of atypical squamous cells of undetermined significance (ASC-US), 1 case of atypical glandular cells-not otherwise specified (AGC-NOS), 1 case of atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H), and 2 cases of atypical glandular cells (AGC). Preoperative tumor markers were elevated in 6 of 12 cases for CA199, 4 of 21 cases for CA125, 3 of 13 cases for human epididymal protein 4 (HE4), and 1 of 19 cases for squamous cell carcinoma antigen (SCC). Among the 21 patients who underwent preoperative ultrasound, 9 cases were suspected to have cervical malignancy, and 1 case of endometrial malignancy was identified. In the 17 patients who underwent pelvic MRI, 9 cases were suspected of having cervical malignancy, along with 2 cases of endometrial malignancy. In the 9 patients who underwent pelvic CT, 7 cases were suspected of cervical malignancy. For preoperative pathology, 9 patients had a single biopsy with a confirmation rate of 33.3% (3/9), 7 patients had 2 biopsies with a confirmation rate of 71.4% (5/7), and 5 patients had 3 biopsies with a confirmation rate of 100% (5/5), leading to an overall confirmation rate of 61.9% (13/21). All patients underwent surgical treatment, with postoperative pathological staging: 3 cases at stage ⅠB1, 1 case at stage ⅠB2, 2 cases at stage ⅠB3, 1 case at stage ⅡA1, 1 case at stage ⅡA2, 2 cases at stage ⅡB, 7 cases at stage ⅢC1p, and 4 cases at stage ⅢC2p. Para-cervical infiltration was observed in 7 cases, with residual cancer at the vaginal stump in 2 cases, deep stromal infiltration (depth ≥1/2) in 19 cases, lymphovascular space invasion in 15 cases, neural invasion in 9 cases, pelvic lymph node metastasis in 11 cases, and para-aortic lymph node metastasis in 4 cases. The follow-up time ranged from 3.5 to 28.0 months (median: 13.5 months), with 13 cases not experiencing recurrence, 7 cases relapsing (6 deceased, 1 alive with tumor), and 1 case lost to follow-up. The overall survival (OS) ranged from 3.5 to 28.0 months [(22.7±1.8) months], and disease-free survival (DFS) ranged from 3.5 to 28.0 months [(20.4±2.3) months]. OS showed no correlation with age, tumor stage, tumor size, depth of stromal infiltration, lymphovascular space invasion, lymph node metastasis, or treatment method (all P >0.05). Cox regression analysis indicated that age, pathological stage, tumor size, depth of stromal infiltration, lymphovascular space invasion, neural invasion, and lymph node metastasis were not associated with DFS or OS (all P >0.05)., Conclusions: GAS is rare in clinical practice, prone to missed or misdiagnosis, with a low early diagnosis rate, strong invasiveness, high recurrence and metastasis rates, and poor prognosis. Clinicians should be vigilant for this disease in HPV-negative patients with significant vaginal discharge and consider performing multiple deep tissue biopsies in conjunction with imaging examinations for early diagnosis.

Background: Independent and valid prognostic predictors for locally advanced gastric cancer (LAGC) patients with non-elevated serum tumor markers (Triple-negative: CA199 < 37U/ml, CEA < 5 µg/ml and CA125 < 35U/ml) before and after neoadjuvant chemotherapy (NACT) remain unclear., Methods: A total of 352 LAGC patients treated with NACT(NLAGC) from two centers were included. Of the 156 were Triple-negative patients. CA72-4 trajectory groupings was defined as longitudinal changes in CA72-4 levels before and after NACT to identify different potential subgroups and to compare recurrence-free survival (RFS) and overall survival (OS) among subgroups. The predictive performance of the nomogram-trajectory was evaluated using the area under the receiver operating characteristic curve(AUC), decision curve analysis, and C-index., Results: In the Triple-negative patients, the Stable group had significantly worse 3-year OS than the Normal, Elevated, and Descend groups(3-year OS: 53.9% vs. 77.9% vs. 73.5% vs. 87.7%;P = 0.002). Cox multivariate analysis showed that CA72-4 trajectory groupings (Stable group: HR:3.442, 95%CI[1.574-7.528], P = 0.002) was an independent prognostic risk factor. In addition, the C-index and AUC values based on the nomogram-trajectory were significantly higher than those of ypTNM staging (C-index: 0.788 vs. 0.719,P < 0.001;AUC: 0.800 vs. 0.667,P < 0.001). Furthermore, The survival analysis revealed that the 3-year OS of the Low-Risk group of nomogram scores was significantly better than that of the High-Risk group(3-year OS:84.7% vs. 29.1%). And the Low-Risk group had the lower cumulative risk of recurrence (P < 0.001)., Conclusion: The CA72-4 trajectory groupings were an independent prognostic factor for NLAGC Triple-negative patients. The predictive efficacy of the Nomogram-trajectory was significantly better than the ypTNM., (© 2024. The Author(s).)

Rationale: Reports of mature cystic teratomas (MCTs) with associated complications and changes in serum cancer antigen levels are rare. Herein, we report a rare case of MCT with associated complications (rupture and malignant transformation), high levels of serum cancer antigens (CA19-9, CA12, and CEA), and surgical therapy., Patient Concerns: An 81-year-old woman was referred to our emergency department because of diffuse abdominal pain and distension for 20 days., Diagnoses: Imaging findings, including transabdominal ultrasonography, computed tomography, and magnetic resonance imaging, revealed a complex solid cystic mass in the lower abdomen. Preoperative laboratory test results showed high levels of serum cancer antigens (CA19-9, CA12, and CEA) in MCT. Histopathological examination of the specimen revealed a MCT with rupture and malignant transformation., Interventions: The patient underwent a total abdominal hysterectomy, bilateral oophorectomy, and partial omentectomy. The patient did not undergo chemotherapy after surgery., Outcomes: The follow-up period was 12 months. The patient recovered well without focal local recurrence or distant metastasis after the surgery., Lessons: The study aims to report a new case of MCT with associated complications (rupture and malignant transformation) and changes in serum cancer antigen levels. Although this tumor presents as a complex solid cystic mass, detection of the intratumoral fat component is a key diagnostic imaging feature. A high level of serum cancer antigen may indicate the malignant transformation of MCT. In this case, surgery was an effective treatment for the MCT., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Ovarian cancer (OC) is the most lethal gynecological cancer in the developed world. Most cases are diagnosed at late stage III-IV with a very low 5-year overall survival rate. Several studies revealed an elevated risk of OC in users of hormone treatment (HT) compared with non-users. The extended duration of HT is a statistically significant risk factor. Carbohydrate antigen or cancer antigen 125 (CA-125) remains the best screening tool for OC; however, its value is limited due to low specificity, leading to unnecessary interventions, surgeries, and psychological harm. Additionally, the variability of ultrasound interpretation highlights the urgent need to develop a univariate index with higher sensitivity and specificity for early diagnosis of OC in women under HT. Herein we critically review the limitations of biomarkers for the detection of OC aiming to suggest an accurate and cost-effective diagnostic ratio that eliminates the impact of body mass index, age, HT, smoking, and benign ovarian diseases on measurements. Numerous studies combine biomarkers such as CA-125, human epididymis protein 4, and thymidine kinase 1 into diagnostic algorithms. Data suggest that the expression of estrogen receptors may have diagnostic and prognostic value, as the estrogen receptor α (ERα):estrogen receptor β (ERβ) ratio is significantly higher in OC than in normal tissue due to ERβ downregulation. A high positive correlation between expression of CA-125 and carbohydrate antigen or cancer antigen 72 - 4 (CA72-4) with ERα and ERβ, respectively, poses that a novel ratio CA-125:CA72-4 could be nodal for monitoring post-menopausal women under HT., (© 2024. The Author(s).)

Background: The distinction between lung adenocarcinoma-associated malignant pleural effusion (MPE) and tuberculous pleural effusion (TPE) continues to pose a challenge. This study sought to assess the supplementary value of tumor markers in enabling a differential diagnosis., Methods: Data concerning tumor markers, which included carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cancer antigen 153 (CA153), cancer antigen 724 (CA724), neuron-specific enolase (NSE), cytokeratin19 fragment (Cyfra21-1), and squamous cell carcinoma antigen (SCCA), in both serum and pleural effusion samples, were retrospectively compiled from lung adenocarcinoma-associated MPE and TPE patients. A comparative analysis of tumor marker concentrations between the two groups was performed to assess diagnostic utility, followed by a multiple logistic regression to control for confounding variables., Results: While gender, serum CA125 and SCCA, and pleural effusion SCCA manifested comparability between the groups, distinctions were noted in patient age and the concentration of other tumor markers in serum and pleural effusion, which were notably elevated in the MPE group. Multiple logistic regression demonstrated a positive association between the risk of lung adenocarcinoma-associated MPE and levels of CEA and CA153 in serum and pleural effusion, as well as Cyfra21-1 in serum (P < 0.05). The odds ratio for CEA surpassed that of CA153 and Cyfra21-1., Conclusions: CEA and CA153 in serum and pleural effusion, and Cyfra21-1 in serum emerge as biomarkers possessing supplementary diagnostic value in distinguishing lung adenocarcinoma-associated MPE from TPE. The diagnostic efficacy of CEA is superior to CA153 and Cyfra21-1. Conversely, the utility of CA125, CA724, NSE, and SCCA appears constrained., Competing Interests: Declaration of Competing Interests The author has no financial or other conflicts of interest to disclose., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Exosomes are nanosized extracellular vesicles released by cells to transport biomolecules such as proteins and RNAs for intercellular communication. Exosomes play important roles in cancer development and metastasis; therefore, they have emerged as potential liquid biopsy biomarkers for cancer screening, diagnosis, and management. Many exosome cargos, including proteins, RNAs, and lipids, have been extensively investigated as biomarkers for cancer liquid biopsy. However, carbohydrates, an important type of biomolecule, have not yet been explored for this purpose. In this study, we reported a new exosomal carbohydrate biomarker, α-linked Thomsen-Friedenreich glycoantigen (TF-Ag-α; Galβ1-3GalNAc-α). To translate our discovery into clinical settings, we developed a surface plasmon resonance-based assay which utilized a unique mAb, JAA-F11, with high specificity to measure the levels of exosomal TF-Ag-α in blood. To the best of our knowledge, we are the first to demonstrate that exosomes carry TF-Ag-α. We detected exosomal TF-Ag-α in as low as 10 μL serum samples from patients with cancer, but in contrast, levels were negligible in those from normal controls. With a total of 233 patients with cancer and normal controls, we showed that exosomal TF-Ag-α detected lung cancer (n = 60) and breast cancer (n = 95) from normal controls (n = 78) with ≥95% and ≥97% accuracy, respectively. These results demonstrated that exosomal TF-Ag-α is a potential liquid biopsy biomarker for cancer diagnosis., Significance: Exosomes or small extracellular vesicles have emerged as potent biomarkers of cancer liquid biopsy. We discovered a new exosomal carbohydrate marker, TF-Ag-α (Galβ1-3GalNAc-α), and showed that exosomal TF-Ag-α detected both lung and breast cancers with >95% accuracy. Our findings demonstrated that exosomal TF-Ag-α is a promising liquid biopsy biomarker for cancer screening and early detection., (©2024 The Authors; Published by the American Association for Cancer Research.)

Objective: We sought to investigate whether the addition of nimotuzumab to gemcitabine would improve the treatment efficacy of advanced pancreatic cancer., Methods: This retrospective analysis involved a total of 98 hospitalized patients harboring advanced pancreatic cancer. Depending on the specific treatment, patients were divided into study groups and control groups. The clinical efficacy, adverse reactions, and follow-up results of the 2 groups were compared, and the physical status, CA724, CA19-9, and CEA levels before and after treatment were monitored and recorded., Results: After treatment, PR ratio, SD ratio, ORR, and DCR in the study group were significantly higher than those in the control group, and PD ratio was significantly lower than that in the control group (P < 0.05) the KPS score after treatment in the study group was markedly higher than that of the control group (P < 0.05). After treatment, however, significantly lower levels of the 3 indicators were observed when compared with the control group (P < 0.05)., Conclusion: Our study highlights a more superior combined efficacy of nimotuzumab and gemcitabine than the control regimen, exhibiting improved survival and reduced levels of CA724, CA19-9, and CEA in patients with advanced pancreatic cancer., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The effects of the dynamics of serum tumor markers (CA72-4, CEA, CA19-9, CA125 and AFP) before and after neoadjuvant chemotherapy (NACT) on the prognosis of gastric cancer(GC) patients remain unclear., Methods: The training set contained 334 GC patients from Fujian Medical University Union Hospital (FJMUUH) and 113 GC patients in Qinghai University Affiliated Hospital (QhUAH) were used as an external validation set. Tumor marker regression load (ΔTMRL) indicator, including ΔCA72-4, ΔCEA, ΔCA19-9, ΔCA125, and ΔAFP, is defined as [(postNACT marker- preNACT marker)/preNACT marker]. Tumor marker regression load score (TMRLS) consists of ΔCA72-4, ΔCEA and ΔCA125. The predictive performance of the nomogram-TMRLS was evaluated using the area under the receiver operating characteristic(ROC) curve(AUC), decision curve analysis(DCA), and C-index., Results: Patients from FJMUUH were divided into two groups, TMRLS-low and TMRLS-high, determined by R package maxstat. Survival analysis revealed a higher 3-year overall survival(OS) in the TMRLS-low than in the TMRLS-high group. The TMRLS-high group who received postoperative adjuvant chemotherapy(AC) showed a significantly higher 3-year OS rate than those who did not. Multivariate COX regression analysis indicated that TMRLS was an independent prognostic factor for OS. A nomogram for predicting OS based on TMRLS showed a significantly higher C-index and AUC than the ypTNM stage. The above results were also found in the QhUAH external validation cohort., Conclusion: TMRLS is a novel independent prognostic factor for GC who underwent NACT and a radical gastrectomy. Furthermore, the TMRLS-high group, who received postoperative AC, may achieve better survival outcomes. Notably, the predictive performance of the nomogram-TMRLS significantly outperformed that of the ypTNM stage., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (© 2024 Elsevier Ltd, BASO ∼ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Aim: To develop a new algorithm for the detection of high-grade serous ovarian cancer (HGSOC)., Methods: Patients diagnosed with HGSOC, borderline ovarian tumours (BOTs) or benign ovarian masses (BOMs) were enrolled between February 2019 and December 2020. Patients with BOTs or BOMs were grouped as non-HGSOC. The cases were divided randomly into a training cohort (two-thirds of cases) and a validation cohort (one-third of cases). Logistic regression was used to find risk factors for HGSOC and to create a new algorithm in the training cohort. Receiver operating characteristic curves were used to compare the diagnostic value of tumour biomarkers. Sensitivity and specificity of tumour markers and the new algorithm were calculated in the training cohort and validation cohort., Results: This study found significant differences in age; BRCA1/2 mutation status; CA125, CA724 and HE4 levels; and Risk of Ovarian Malignancy Algorithm score between the two groups.Logistic regression analysis showed that CA125 and BRCA1/2 were risk factors for HGSOC. A new algorithm combining CA125 and BRCA1/2 increased the specificity of CA125 for diagnosis of HGSOC. The new algorithm had sensitivity of 81.08% and specificity of 93.10% in the training cohort., Conclusion: The new algorithm using CA125 and BRCA1/2 helped to distinguish between patients with HGSOC and patients with non-HGSOC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: To date, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) have been widely used for the screening, diagnosis and prediction of biliary tract cancer (BTC) patients. However, few studies with large sample sizes of carbohydrate antigen 50 (CA50) were reported in BTC patients., Methods: A total of 1121 patients from the Liver Cancer Clin-Bio Databank of Anhui Hepatobiliary Surgery Union between January 2017 and December 2022 were included in this study (673 in the training cohort and 448 in the validation cohort): among them, 458 with BTC, 178 with hepatocellular carcinoma (HCC), 23 with combined hepatocellular-cholangiocarcinoma, and 462 with nontumor patients. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the diagnostic efficacy and clinical usefulness., Results: ROC curves obtained by combining CA50, CA19-9, and AFP showed that the AUC value of the diagnostic MODEL 1 was 0.885 (95% CI 0.856-0.885, specificity 70.3%, and sensitivity 84.0%) in the training cohort and 0.879 (0.841-0.917, 76.7%, and 84.3%) in the validation cohort. In addition, comparing iCCA and HCC (235 in the training cohort, 157 in the validation cohort), the AUC values of the diagnostic MODEL 2 were 0.893 (95% CI 0.853-0.933, specificity 96%, and sensitivity 68.6%) in the training cohort and 0.872 (95% CI 0.818-0.927, 94.2%, and 64.6%) in the validation cohort., Conclusion: The model combining CA50, CA19-9, and AFP not only has good diagnostic value for BTC but also has good diagnostic value for distinguishing iCCA and HCC., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: To investigate the clinical characteristics and prognosis of bone metastasis of gastric cancer, analyze the influencing factors of bone metastasis and the effects of different treatment methods, and provide a basis for early detection and treatment optimization of bone metastasis of gastric cancer. Methods: A total of 142 gastric cancer patients with bone metastasis admitted to the First Hospital of Lanzhou University from January 2011 to December 2021 were enrolled, including 60 cases of simple bone metastasis and 82 cases of bone metastasis combined with extraosseous metastasis. 142 patients with stage Ⅲgastric cancer without distant metastasis and 142 gastric cancer patients with visceral metastasis admitted to this hospital during the same period were also enrolled for comparison. Logistic regression analysis was used to determine the influencing factors of bone metastasis, and the Cox proportional hazards regression model was used to evaluate the influencing factors of overall survival (OS) of patients with bone metastasis. Results: Among the 142 patients with bone metastasis, poorly differentiated adenocarcinoma was the main type (123 cases), and 45 patients had simultaneous bone metastasis. Rib metastasis (100 cases), spine metastasis (88 cases), and pelvis metastasis (84 cases) were more common. A total of 110 patients had multiple bone metastasis, and 82 patients had extraosseous metastasis. Results of the stage Ⅲ gastric cancer group, the visceral metastasis group, the bone metastasis group, and the bone metastasis with extraosseous metastasis group were compared. There were significant differences in age, degree of differentiation, Borrmann type, alkaline phosphatase, lactate dehydrogenase, serum calcium, alanine aminotransferase, aspartate aminotransferase, creatine kinase isoenzyme, lymphocyte, hemoglobin, platelet, CEA, CA19-9, and CA724 (all P <0.05). Multivariate logistic regression analysis showed that Borrmann type was an independent protective factor of bone metastasis of gastric cancer (type 3: OR =0.07, 95% CI : 0.01-0.64, P =0.018). Alkaline phosphatase ( OR =2.54, 95% CI : 1.07-6.01, P =0.034), serum calcium ( OR =2.71, 95% CI : 1.15-6.41, P =0.023), creatine kinase isoenzyme ( OR =16.33, 95% CI : 1.83-145.58, P =0.012), platelet ( OR =10.08, 95% CI :1.89-53.85, P =0.007), and CA19-9 ( OR =2.40, 95% CI : 1.14-5.05, P =0.021) were independent risk factors of bone metastasis of gastric cancer. The median OS of the stage Ⅲ gastric cancer group, the visceral metastasis group, the bone metastasis group, and the bone metastasis with extrabony group were 47, 13, 18, and 6 months, respectively, and the difference was statistically significant ( P <0.001). The median OS of patients with bone metastasis only who underwent primary tumor surgery was 33 months, better than 6 months of patients without surgery ( P =0.048). Multivariate Cox regression analysis showed that extraosseous metastasis ( HR =2.45, 95% CI : 1.56-3.85, P <0.001) and decreased hemoglobin ( HR =1.54, 95% CI : 1.02-2.34, P =0.042) were independent risk factors of OS of gastric cancer patients with bone metastasis. Conclusions: The prognosis of gastric cancer patients with bone metastasis alone is significantly better than that of other stage Ⅳ patients. For such patients, surgery on the primary site combined with chemotherapy after full evaluation may prolong the survival time.

Objective: This study aims to develop a predictive model for the detection of gastric cancer risk utilizing non-invasive parameters and to assess the model's effectiveness in risk stratification for gastric cancer (GC)., Methods: A case-control study was conducted among inpatients with various gastric diseases. These individuals were categorized into two groups: the gastric cancer group (138 cases) and the chronic non-atrophic gastritis (CNAG) group (319 cases). We employed a comprehensive panel of hematological, biochemical, and coagulation parameters derived from routine blood tests. Random Forest and Logistic regression analysis was used for feature selection and model building. Statistical analyses were performed using R version 4.2.3., Results: Logistic regression analysis was employed to establish risk prediction models for GC, incorporating variables such as D-dimer, carcinoembryonic antigen (CEA), carbohydrate antigen 724 (CA724), and hemoglobin (HGB). A visual nomogram was generated as the final prediction model. The area under the receiver operating characteristic curve (AUC) for the training and test sets were 0.8093 [95% confidence interval (CI), 0.7541-0.8644], and 0.8076 [95% CI 0.7237-0.8915], respectively. Furthermore, we have developed an HTML file, featuring the Logistic equation, which enables real-time assessment of GC risk scores., Conclusion: The performance of this predictive model demonstrates its adequacy, making it a valuable and cost-effective noninvasive tool for identifying early gastric cancer (EGC) in patients. Consequently, this model may facilitate the implementation of targeted preventive and intervention strategies in clinical practice., (© 2024 by the Association of Clinical Scientists, Inc.)

Purpose: This study aimed to assess the utility of 6 serum tumor markers in prognosis between gastric adenocarcinoma and gastric signet ring cell carcinoma (SRCC)., Methods: A cohort of 3131 cases of gastric adenocarcinoma and 275 cases of gastric SRCC was assembled. The serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125, alpha fetoprotein (AFP), carbohydrate antigen 242 (CA242), and carbohydrate antigen 724 (CA724) were measured in all cases. The study analyzed the association between the levels of these 6 tumor markers and the prognosis of gastric adenocarcinoma and SRCC., Results: The study revealed that gastric SRCC exhibited lower concentrations of CEA (P < .001) and CA19-9 (P = .002), along with reduced positive rates of CEA (P = .041), CA19-9 (P = .003), AFP (P < .001), and CA242 (P = .006), while displaying higher positive rates of CA724 (P = .024) than gastric adenocarcinoma. Nevertheless, the receiver operating characteristic curve demonstrated that serum tumor markers did not hold clinical significance in differentiating between gastric adenocarcinoma and SRCC. Survival analysis substantiated that the combined criteria of serum tumor markers stood as an independent risk factor for both gastric adenocarcinoma and SRCC. Notably, the nomogram indicated that serum tumor markers exerted a more substantial influence on the prognosis of gastric adenocarcinoma than on gastric SRCC., Conclusion: The study concluded that the combined criteria of serum tumor markers emerge as independent risk factors for both subtypes of gastric cancer. Furthermore, this combined approach exhibited enhanced efficacy in prognosticating the outcome of gastric adenocarcinoma compared with gastric SRCC., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Background: Owing to the subtlety of initial symptoms associated with gastric cancer (GC), the majority of patients are diagnosed at later stages. Given the absence of reliable diagnostic markers, it is imperative to identify novel markers that exhibit high sensitivity and specificity. Circular RNA, a non-coding RNA, plays an important role in tumorigenesis and development and is well expressed in body fluids., Aims: In this study, we aimed to identify hsa&#95;circ&#95;0000231 as a new biomarker for the diagnosis of GC and to assess its clinical diagnostic value in serum., Methods and Results: The stability and correctness of hsa&#95;circ&#95;0000231 was determined by agarose gel electrophoresis, Rnase R assay and Sanger sequencing. Real-time quantitative polymerase chain reaction (qRT-PCR) was designed to discover the expression level of hsa&#95;circ&#95;0000231 and whether it has dynamic serum monitoring capability. The correlation between hsa&#95;circ&#95;0000231 and clinicopathological parameters was analyzed by collecting clinical and pathological data from GC patients. In addition, diagnostic efficacy was assessed by constructing receiver operating characteristic curves (ROC). Hsa&#95;circ&#95;0000231 exhibits a stable and consistently expressed structure. In GC serum, cells, and tissues, it demonstrates reduced expression levels. Elevated expression levels observed postoperatively suggest its potential for dynamic monitoring. Additionally its expression level correlates with TNM staging and neuro/vascular differentiation. The area under ROC curve (AUC) for hsa&#95;circ&#95;0000231 is 0.781, indicating its superior diagnostic value compared to CEA, CA19-9, and CA72-4. The combination of these four indicators enhances diagnostic accuracy, with an AUC of 0.833., Conclusions: The stable expression of hsa&#95;circ&#95;0000231 in the serum of gastric cancer patients holds promise as a novel biomarker for both the diagnosis and dynamic monitoring of GC., (© 2024 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Background: Carbohydrate antigen 72-4 (CA72-4) is a mucin-like, tumor-associated glycoprotein. Its elevation in serum has been found to be associated with various carcinomas. The purpose of this study was to evaluate the analytical performance of the Architect chemiluminescent immunoassay CA72-4 on the Architect i2000sr platform and to determine the reference interval (RI) of CA72-4 for the Chinese Han population in the city of Wuhan., Methods: We evaluated the precision, analytical sensitivity, linearity and interference according to the guidelines of the Clinical Laboratory Standardization Institute. Additionally, the Abbott Architect i2000sr CA72-4 assay was compared to the Roche Cobas E602 CA72-4 assay. A total of 448 healthy individuals were selected to determine the RIs of CA72-4., Results: The assay had an imprecision of 1.38% - 2.63% within runs, 1.41% - 2.73% between runs and a total imprecision of 2.54% - 4.10%. The limit of blank, limit of detection and limit of quantitation concentrations were 0.19 U/mL, 0.21 U/mL, and 0.21 U/mL. Linearity was confirmed across the entire measurable range. Additionally, the carryover was less than 0.065%. Interferences with hemoglobin, conjugated bilirubin and lipemia were acceptable with changes of less than 10%. A correlation coefficient of 0.9450 was determined through the method comparison experiment (95% CI 0.9318 - 0.9557). The RI for serum CA72-4 in the Han population was established as an upper limit, 11.13 U/mL (90% CI 9.39 - 12.99) by using the Abbott Architect i2000sr system., Conclusions: This study establishes a RI for the Chinese Han population in Wuhan using the Abbott Architect i2000sr CA72-4 assay and demonstrates an analytical performance for clinical use.

The simultaneous identification and detection of multiple tumor markers provide more pathological information for the accurate diagnosis of cancer. In this study, a novel glycosyl imprinted sensor for the simultaneous detection of tumor markers CA19-9 and CA72-4 was prepared by combining the specific recognition of the glycosylated imprinting technique and lectin-characteristic glycan chains. The imprinted membrane was fabricated by electropolymerization using the characteristic glycopeptide STn on the surface of CA72-4 and the characteristic glycopeptide SLe a on the surface of CA19-9 as template molecules and 2-aminophenylboronic acid as the functional monomer. To further improve the recognition efficiency, the specific binding of lectins to glycosyl chains was introduced. Sambucus nigra agglutinin I (SNA I) was labeled with cysteine, and Maackia amurensis lectin II (MAL II) was labeled with ferrocene. According to the specific binding of SNA to the Neu5Acα2-6GalNAcα-glycan chain in STn and MAL to α2, 3 sialic acid in SLe a , CA72-4, and CA19-9 could be determined, respectively, after recombination between the glycosyl groups and GIP. The sensor shows high sensitivity to CA72-4 and CA19-9 in the concentration range of 0.005-200.0 U/mL, and it has been successfully applied to the detection of CA72-4 and CA19-9 in serum samples. The sensor provides a simple, fast, and low-cost alternative for accurate diagnosis of gastric cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The objective of the current study was to look at the levels of blood micro ribonucleic acid- (miR-) 497, carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 24-2, and hepatitis B surface antigen (HBsAg) in patients with colorectal cancer (CRC), as well as the clinical importance of these markers in CRC patients. The serum levels of miR-497, CEA, CA24-2, and HBsAg were compared between 60 patients with CRC (observation group) and another 60 patients with colorectal polyps (control group). The 4 indicators in patients with lymph node metastasis and liver metastasis were compared. The diagnostic effects of 4 detection methods and the combined detection were analyzed, and the influence of 4 indicators on the 5-year cumulative survival rate of patients was discussed. The results showed that the serum levels of miR-497 and HBsAg were lower, and the levels of CEA and CA24-2 were higher in the observation group ( P < 0.05). The combined detection had the best diagnostic effect, and CEA alone had the best prediction effect. The serum level of miR-497 was significantly lower in patients with lymphatic metastasis, with the significantly higher levels of CEA and CA24-2 ( P < 0.05). The HBsAg level of patients with liver metastases was greatly lower than that of patients without liver metastases ( P < 0.05). The 5-year cumulative survival rate of patients with high levels of CEA and CA24-2 was significantly lower than that of patients with low level of CEA. The 5-year cumulative survival rate was lower in patients with low level of HBsAg, but the difference was small. The 5-year cumulative survival rate of patients with elevated serum miR-497 was observably lower. In conclusion, combined detection could diagnose CRC more accurately. Serum miR-497, CEA, and CA24-2 were important in the diagnosis of lymph node metastasis of CRC. HBsAg did a better job of predicting liver metastases in CRC patients. High level of CEA significantly reduced the cumulative survival rate of CRC patients and could predict the long-term survival rate of patients. Serum levels of miR-497, CEA, CA24-2, and HBsAg played a positive role in the diagnosis and evaluation of CRC and could identify lymph node and liver metastases, having a high clinical guidance value., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 Yan Liu and Jie Chen.)

Purpose: To find a useful disease marker for early diagnosis of gastric cancer, we tried to explore the expression of serum miR-181, miR-652, and carbohydrate antigen 72-4 (CA72-4)., Patients and Methods: According to clinical pathologic stages, 112 patients with gastric cancer were divided into early gastric cancer group (n = 60) and advanced gastric cancer group (n = 52), stage I-II (n = 65), and stage III-IV (n = 47). Another 50 cases of gastric benign lesions and 40 healthy controls were also selected. Real-time quantitative PCR together with chemiluminescence were applied to detect expression levels. ROC curve was applied to judge their diagnostic efficiency. Pearson's correlation analysis was put into use to investigate the relevance of three indicators., Results: Compared with benign lesions group and control group, significantly higher expression levels were found in patients of gastric cancer (all p < 0.001). Similarly, compared with early gastric cancer group, significantly higher expression levels were found in advanced gastric cancer group (all p < 0.001). The same result was also found in stage III-IV (all p < 0.001). The best cutoff values were 0.93, 2.38, and 16.94 U/ml, respectively. The area under the curve (0.917, 95%CI: 0.856-0.975) of the three combined diagnosis of early gastric cancer was the largest, and its sensitivity and specificity were 92.5% and 86.8%. And miR-181 and miR-652 were positively correlated with CA72-4 (r = 0.772, p < 0.001, r = 0.853, p < 0.001)., Conclusion: Serum miR-181, miR-652, and CA72-4 are closely linked to the occurrence and development of gastric cancer. Combination of three indicators has diagnostic value for early gastric cancer., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

The objective of this study was to analyze the value of artificial intelligence algorithm-based computerized tomography (CT) image combined with serum tumor markers for diagnoses of pancreatic cancer. In the study, 68 hospitalized patients with pancreatic cancer were selected as the experimental group, and 68 hospitalized patients with chronic pancreatitis were selected as the control group, all underwent CT imaging. An image segmentation algorithm on account of two-dimensional (2D)-three-dimensional (3D) convolution neural network (CNN) was proposed. It also introduced full convolutional network (FCN) and UNet network algorithm. The diagnostic performance of CT, serum carbohydrate antigen-50 (CA-50), serum carbohydrate antigen-199 (CA-199), serum carbohydrate antigen-242 (CA-242), combined detection of tumor markers, and CT-combined tumor marker testing (CT-STUM) for pancreatic cancer were compared and analyzed. The results showed that the average Dice coefficient of 2D-3D training was 84.27%, which was higher than that of 2D and 3D CNNs. During the test, the maximum and average Dice coefficient of the 2D-3D CNN algorithm was 90.75% and 84.32%, respectively, which were higher than the other two algorithms, and the differences were statistically significant ( P < 0.05). The penetration ratio of pancreatic duct in the experimental group was lower than that in the control group, the rest were higher than that in the control group, and the differences were statistically significant ( P < 0.05). CA-50, CA-199, and CA-242 in the experimental group were 141.72 U/mL, 1548.24 U/mL, and 83.65 U/mL, respectively, which were higher than those in the control group, and the differences were statistically significant ( P < 0.05). The sensitivity, specificity, positive predictive value, and authenticity of combined detection of serum tumor markers were higher than those of CA-50, CA-199, and CA-242, and the differences were statistically significant ( P < 0.05). The results showed that the proposed algorithm 2D-3D CNN had good stability and image segmentation performance. CT-STUM had high sensitivity and specificity in diagnoses of pancreatic cancer., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Zhengmei Qiao et al.)

Background: Serum indicators AFP, CA50, CA125, CA153, CA19-9, CEA, f-PSA, SCC-Ag have been confirmed as tumor markers (TMs). We conducted a genome-wide association study on 8 tumor markers of our 427 Han population in southern China, in order to identify genetic loci that are significantly associated with the level of 8 tumor markers., Methods: We use Gene Titan multi-channel instrument and Axiom Analysis Suite 6.0 software for genotyping. We used IMPUTE2 software for imputation, and 1000 Genomes Project (Phase 3) was used as haplotype reference. After necessary quality control and statistical analysis, genetic loci genome-wide associated with TMs (p < 5E-8) will be identified. Finally, we selected Top SNPs (p < 5E-7) from the GWAS results for replication test. We used SPSS software to draw the distribution box plots of serum TMs under different genotypes of significant loci., Results: The results showed that there were only MUC1 (mucin 1)-rs4072037 significantly genome-wide associated with CA153 (p = 1.28E-18). However, we found that a total of 30 genetic loci have a suggestively significant genome-wide association with the level of 8 serum tumor markers (p < 5E-6). Then 3 Top SNPs (p < 5E-7) were selected for replication verification. The results showed that MUC1-rs4072037 was still significantly associated with CA153 in another population (p = 3.73E-08). Comparing with the TT genotype of rs4072037, the CA153 level was higher under CC or CT genotype of rs4072037., Conclusion: MUC1-rs4072037 is significantly genome-wide associated with CA153 level. There are 30 genetic loci suggestively genome-wide associated with level of tumor markers among the Han population from Southern China., (© 2022. The Author(s).)

Background: Borderline resectable pancreatic cancer (BRPC) is a category of pancreatic cancer that is anatomically widely spread, and curative resection is uncommon with upfront surgery. Intensity-modulated radiation therapy (IMRT) is a form of radiation therapy that delivers precise radiation to a tumor while minimizing the dose to surrounding normal tissues. Here, we conducted a phase 2 study to estimate the curability and efficacy of neoadjuvant chemoradiotherapy using IMRT (NACIMRT) for patients with BRPC with arterial abutment (BRPC-A)., Methods: A total of 49 BRPC-A patients were enrolled in this study and were treated at our hospital according to the study protocol between June 2013 and March 2021. The primary endpoint was microscopically margin-negative resection (R0) rates and we subsequently analyzed safety, histological effect of the treatment as well as survivals among patients with NACIMRT., Results: Twenty-nine patients (59.2%) received pancreatectomy after NACIMRT. The R0 rate in resection patients was 93.1% and that in the whole cohort was 55.1%. No mortality was encountered. Local therapeutic effects as assessed by Evans classification showed good therapeutic effect (Grade 1, 3.4%; Grade 2a, 31.0%; Grade 2b, 48.3%; Grade 3, 3.4%; Grade 4, 3.4%). Median disease-free survival was 15.5 months. Median overall survival in the whole cohort was 35.1 months. The only independent prognostic pre-NACIMRT factor identified was serum carbohydrate antigen 19-9 (CA19-9) > 400 U/ml before NACIMRT., Conclusions: NACIMRT showed preferable outcome without significant operative morbidity for BRPC-A patients. NACIMRT contributes to good local tumor control, but a high initial serum CA19-9 implies poor prognosis even after neoadjuvant treatment., Trial Registration: UMIN-CTR Clinical Trial: https://upload.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000011776 Registration number: UMIN000010113. Date of first registration: 01/03/2013., (© 2022. The Author(s).)

Background: The ratio of serum apolipoprotein B (apoB) to apolipoprotein A-I (apoAI) had been reported as a prognostic factor in colorectal cancer. This retrospective study aimed to assess the implication of apoB-to-apoAI ratio in predicting liver metastasis from rectal cancer (RC)., Methods: The clinical data of 599 locally advanced RC patients treated with chemoradiotherapy followed by surgery were reviewed. Serum apoAI, apoB and apoB-to-apoAI ratio were analyzed for their correlation with the liver-metastasis-free, other-metastasis-free and overall survivals, together with the pretreatment and postsurgical pathoclinical features of the patients. Univariate and multivariate survival analyses were realized through the Kaplan-Meier approach and Cox model, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for independent predictors., Results: Carbohydrate antigen 19 - 9 ≥ 26.3 U/ml, apoB-to-apoAI ratio ≥ 0.63, tumor regression grade 5 - 3, pT4 and pN + stage emerged as independent predictors of poorer liver-metastasis-free survival. The hazard ratios were 1.656 (95% CI, 1.094-2.506), 1.919 (95% CI, 1.174-3.145), 1.686 (95% CI, 1.053-2.703), 1.890 (95% CI, 1.110-3.226) and 2.012 (95% CI, 1.314-2.077), respectively. Except apoB-to-apoAI ratio, the other 4 factors were also independent predictors of poorer other-metastasis-free and overall survivals. And the independent predictors of poorer overall survival also included age ≥ 67 years old, distance to anal verge < 5 cm., Conclusions: Serum apoB-to-apoAI ratio could be used as a biomarker for prediction of liver metastasis risk in locally advanced RC., (© 2021. The Author(s).)

Background: Xanthogranulomatous cholecystitis (XGC) is an extremely rare entity. Due to XGC's clinical and radiological resemblance to gallbladder carcinoma (GBC), intraoperative frozen section during cholecystectomy is often performed to exclude the diagnosis of GBC. Our study is aiming to find a noninvasive indicator of XGC. To our knowledge, this is the largest XGC cohort ever studied., Methods: This study retrospectively collected clinical characteristics, serological tests, and imaging features of 150 GBC patients and 90 XGC patients. The diagnosis of these 150 GBC patients and 90 XGC patients was based on intraoperative frozen section histopathology. T-test was utilized to compare differences between XGC and GBC. Receiver operating characteristic (ROC) curve was conducted and the area under the curve (AUC) was managed to evaluate the validity., Results: The carcinoembryonic antigen (CEA) level in blood tests was significantly elevated in GBC patients than in XGC patients (p = 0.007). The presence of submucosal hypo-attenuated nodules (80% in XGC, 16% in GBC, p < 0.001), low density border (60% in XGC, 21% in GBC, p = 0.001), and nodular thickening in the bottom of the gallbladder with calcification (70% in XGC, 37% in GBC, p = 0.004) is significantly associated with XGC patients, whereas massive hilar infiltration (0% in XGC, 21% in GBC, p < 0.001), multiple lymph nodes in the hilar area (10% in XGC, 72% in GBC, p = 0.001), and gallbladder mucosal line continuity (50% in XGC, 95% in GBC, p = 0.002) are highly associated with GBC patients. The ROC curve was performed and the gallbladder mucosal line continuity (AUC = 0.708) and the AUC of low density border around the occupation (AUC = 0.654) showed a good prediction of XGC., Conclusions: Gallbladder mucosal line continuity and low density border around the occupation presented good indication value for the diagnosis of XGC. Our study proposed a noninvasive differential diagnosis method for XGC and GBC., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: It was previously shown in three subpopulations that subjects not identified with colorectal cancer (CRC) at bowel endoscopy, but with increased serological cancer-associated protein biomarker levels had an increased risk of being diagnosed with subsequent malignant diseases., Objective: The aim of the present study was to perform a pooled analysis of subjects from the three subpopulations and subsequently validate the results in an independent study. The study population denoted the training set includes N = 4,076 subjects with symptoms attributable to CRC and the independent validation set N = 3,774 similar subjects., Methods: Levels of CEA, CA19-9, TIMP-1 and YKL-40 were determined in blood samples collected prior to diagnostic bowel endoscopy. Follow-up of subjects not diagnosed with CRC at endoscopy, was ten years and identified subjects diagnosed with primary intra- or extra-colonic malignant diseases. The primary analysis was time to a newly diagnosed malignant disease and was analyzed with death as a competing risk in the training set. Subjects with HNPCC or FAP were excluded. The cumulated incidence was estimated for each biomarker and in a multivariate model. The resulting model was then validated on the second study population., Results: In the training set primary malignancies were identified in 515 (12.6%) of the 4,076 subjects, who had a colorectal endoscopy with non-malignant findings. In detail, 33 subjects were subsequently diagnosed with CRC and 482 subjects with various extra-colonic cancers. Multivariate additive analysis of the dichotomized biomarkers demonstrated that CEA (HR = 1.50, 95% CI:1.21-1.86, p < 0.001), CA19-9 (HR = 1.41, 95% CI:1.10-1.81, p = 0.007) and TIMP-1 (HR = 1.25 95% CI: 1.01-1.54, p = 0.041) were significant predictors of subsequent malignancy. The cumulated incidence at 5 years landmark time was 17% for those subjects with elevated CEA, CA19-9 and TIMP-1 versus 6.7% for those with low levels of all. When the model was applied to the validation set the cumulated 5-year incidence was 10.5% for subjects with elevated CEA, CA19-9 and TIMP-1 and 5.6% for subjects with low levels of all biomarkers. Further analysis demonstrated a significant interaction between TIMP-1 and age in the training set. The age dependency of TIMP-1 indicated a greater risk of malignancy in younger subjects if the biomarker was elevated. This observation was validated in the second set., Conclusion: Elevated cancer-associated protein biomarker levels in subjects with non-malignant findings at large bowel endoscopy identifies subjects at increased risk of being diagnosed with subsequent primary malignancy. CEA, CA19-9 and TIMP-1 were significant predictors of malignant disease in this analysis. TIMP-1 was found dependent on age. The results were validated in an independent symptomatic population.

A retrospective study was conducted to analyze which translational therapy, palliative chemotherapy and surgery is the best treatment for locally advanced and advanced pancreatic cancer, and to screen out the dominant population for the best treatment. A total of 83 patients with pancreatic cancer, including locally advanced and advanced pancreatic cancer, who had lost the opportunity for radical surgery and were admitted to Zhejiang Provincial People's Hospital between January 2015 and July 2021 were collected. A total of 39 patients received palliative chemotherapy, 25 patients received conversion therapy and 19 patients tried surgery at the first visit. We conducted survival follow-up and prognostic evaluation of 83 patients. The median overall survival (mOS) and median progression-free survival (mPFS) of 25 pancreatic cancer patients who received conversion therapy were longer than those of pancreatic cancer patients who received palliative chemotherapy (mOS: 16 months vs. 9 months, P = 0.001; mPFS: 11 months vs. 7.5 months, P = 0.038) and surgery (mOS: 16 months vs. 9 months, P = 0.018; mPFS: 11 months vs. 5.5 months, P < 0.001). Multivariate and Kaplan-Meier analysis showed that age, distant metastasis, and the degree of CA199 declined after chemotherapy were independent factors affecting overall survival (OS) of pancreatic cancer patients who received conversion therapy. Conversion therapy can improve OS and progression-free survival in patients with locally advanced or advanced pancreatic cancer to a certain extent. Some patients with advanced pancreatic cancer have surprising results after receiving conversion therapy., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Immune checkpoint inhibitors have shown great promise in treating patients with mismatch repair deficient/microsatellite instability high (dMMR/MSI-H) colorectal cancer (CRC). Although single-agent pembrolizumab has been approved for first-line treatment of dMMR/MSI-H metastatic CRC, combination therapy with cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) inhibition (ipilimumab/nivolumab) has reported higher response rates. It is unclear whether patients who progress on PD-1 inhibition will respond to CTLA-4 blockade. Here, we report a case series of three patients with dMMR/MSI-H mCRC, where a durable and ongoing response to nivolumab with ipilimumab was achieved after initial progression with pembrolizumab monotherapy. Blood-based biomarkers such as carcinoembryonic antigen and CA 19-9 were employed to assess treatment response and monitor disease progression along with circulating tumor DNA (ctDNA). Our findings indicate ctDNA's potential to accurately monitor response to therapy and detect disease progression, as validated by standard imaging. This case series demonstrates that CTLA-4 rescue is worthy of additional investigation as a treatment strategy after progression on PD-1 blockade in patients with dMMR/MSI-high mCRC. Our data support the utilization and expansion of clinical studies with combination therapies and using ctDNA kinetics as early dynamic marker for therapy response assessment., Competing Interests: Competing interests: PMK Consultancy/Advisory Board: Taiho Oncology, Ipsen, Natera, Foundation Medicine; Research/Trial Support (to institution): BMS, Celgene, AstraZeneca, BTG, Advanced Accelerator Applications, Array Biopharma. AG: Research funding from Array BioPharma, Bayer, Boston Biomedical, Daiichi Sankyo, Eisai, Genentech/Roche, Lilly, Pfizer. SEK: Research funding from Amgen, Array BioPharma, Biocartis, EMD Serono, Genentech/Roche, Guardant Health, Lilly, MedImmune, Novartis, Sanofi. GB, MK, VNA, AKM, MM, PO, PRB and AA are employees of Natera with stock/options to own stock in the company., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: The dynamic monitoring of perioperative carcinoembryonic antigen (CEA) is recommended by current colorectal cancer (CRC) guidelines, while the benefits of additional measurements of carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 125 (CA125) have remained controversial., Methods: This retrospective longitudinal cohort included 3539 CRC patients who underwent curative resection. Distinct trajectory groups were identified by the latent class growth mixed model. Patients were grouped into subgroups jointly by CEA, CA19-9, and CA125 according to preoperative levels and longitudinal trajectories, respectively. The end points were overall survival (OS) and recurrence-free survival (RFS)., Findings: Three distinct trajectory groups were characterized for serum CEA, CA19-9, and CA125: low-stable, early-rising, and later-rising. Jointly, patients were grouped into six preoperative (trajectory) joint groups. Compared with the three-low group, the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) associated with death were 1.87 (1.29-2.70), 3.82 (2.37-6.17), 1.87 (0.97-3.61), 2.81 (1.93-4.11), and 4.99 (2.80-8.86) for the CEA-high, CA19-9-high, CA125-high, two-high, and three-high group, respectively. And compared with the three-stable trajectory group, the corresponding HRs (95% CIs) were 1.59 (1.10-2.30), 1.55 (0.77-3.10), 6.25 (4.02-9.70), 4.05 (2.73-6.02), and 12.40 (5.77-26.70) for the five rising trajectory groups, respectively. Similar associations between joint groups and RFS were observed. Notably, the trajectory joint group still had prognostic significance after adjusting for preoperative levels. The CA19-9-high group (HR: 3.82, 95% CI: 2.37-6.17) was associated with higher risk of death than the two-high group (HR: 2.81, 95% CI: 1.93-4.11). Likewise, for the CA125-rising trajectory group and two-rising trajectory group, the HRs (95% CIs) were 6.13 (3.75-10.00) and 3.99 (2.63-6.05) for death, and 3.08 (2.07-4.58) and 2.10 (1.52-2.90) for recurrence., Interpretation: In addition to CEA, the dynamic measurements of CA19-9 and CA125 are recommended to monitor the prognosis of CRC patients., Funding: National Natural Science Foundation of China [81973147, 82001986, 81960592, 82073569, 81660545]., Competing Interests: Declaration of Competing Interest All authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background/aim: The clinical benefit of conversion surgery (CS) after chemotherapy remains unclear for stage IV gastric cancer (GC) patients. This study aimed to investigate the prognostic factors used to determine whether CS is a promising therapeutic strategy., Patients and Methods: We retrospectively analyzed data from 156 patients diagnosed with unresectable stage IV GC who underwent chemotherapy as the initial treatment, including 40 patients who had R0 resection in CS., Results: The median survival time of the CS patients was significant longer than that of patients who underwent chemotherapy alone. A multivariate analysis identified only pN3 as an independent prognostic factor in CS patients. Among the differentiated tumor type patients, carbohydrate antigen 19-9 (CA19-9) levels were significantly higher in pN3 patients than in pN0-2 patients before chemotherapy. Among undifferentiated tumor type patients, pN3 patients had a significantly lower tumor size ratio (before chemotherapy/before surgery) than pN0-2 patients., Conclusion: Although it is clinically difficult to diagnose lymph node metastasis using preoperative examinations, CA19-9 levels and tumor size ratios may be preoperative indicators for predicting pN3, which is associated with a poor prognosis in CS., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

In this study, we explored the predictive value of serum microRNA (miRNA) expression for early tumor progression during FOLFIRINOX chemotherapy and its association with overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). A total of 132 PDAC patients of all disease stages were included in this study, of whom 25% showed progressive disease during FOLFIRINOX according to the RECIST criteria. MiRNA expression was analyzed in serum collected before the start and after one cycle of chemotherapy. In the discovery cohort ( n = 12), a 352-miRNA RT-qPCR panel was used. In the validation cohorts (total n = 120), miRNA expression was detected using individual RT-qPCR miRNA primers. Before the start of FOLFIRINOX, serum miR-373-3p expression was higher in patients with progressive disease compared to patients with disease control after FOLFIRINOX (Log2 fold difference (FD) 0.88, p = 0.006). MiR-194-5p expression after one cycle of FOLFIRINOX was lower in patients with progressive disease (Log2 FD -0.29, p = 0.044). Both miRNAs were predictors of early tumor progression in a multivariable model including disease stage and baseline CA19-9 level (miR-373-3p odds ratio (OR) 3.99, 95% CI 1.10-14.49; miR-194-5p OR 0.91, 95% CI 0.83-0.99). MiR-373-3p and miR-194-5p did not show an association with OS after adjustment for disease stage, baseline CA19-9, and chemotherapy response. In conclusion, high serum miR-373-3p before the start and low serum miR-194-5p after one cycle are associated with early tumor progression during FOLFIRINOX.

Introduction: Gastric cancer (GC) diagnosis in late stages and high mortality rates are the main issues that require new noninvasive molecular tools. We aimed to assess somatic mutational profiles in GC tissue and plasma cell-free DNA (cfDNA), evaluate their concordance rate, and analyze the role of multilayer molecular profiling to predict disease state and prognosis., Methods: Treatment-naive GC patient group (n = 29) was selected. Whole exome sequencing (WES) of GC tissue was performed, and a unique 38-gene panel for deep targeted sequencing of plasma cfDNA was developed. Oncoproteins were measured by enzyme-linked immunosorbent assay, and other variables such as tumor mutational burden and microsatellite instability were evaluated using WES data., Results: The yield of cfDNA was increased 43.6-fold; the integrity of fragments was decreased in GC compared with controls. WES analysis of cancerous tissue and plasma cfDNA (targeted sequencing) mutational profiles revealed 47.8% concordance. The increased quantity of GC tissue-derived alterations detected in cfDNA was associated with worse patients' survival. Analysis of importance of multilayer variables and receiver operating characteristic curve showed that combination of 2 analytes: (i) quantity of tissue matching alterations and (ii) presence of any somatic alteration in plasma cfDNA resulted in area under curve 0.744 when discriminating patients with or without distant metastasis. Furthermore, cfDNA sequence alterations derived from tumor tissue were detected in patients who had even relatively small GC tumors (T1-T2)., Discussion: Our results indicate that quantitative and qualitative cfDNA mutational profile analysis is a promising tool for evaluating GC disease status or poorer prognosis., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: To develop and validate multivariate models integrating endoscopic biopsy, tumor markers, and CT findings based on late arterial phase (LAP) to predict serosal invasion in gastric cancer (GC)., Methods: The preoperative differentiation degree, tumor markers, CT morphological characteristics, and CT value-related and texture parameters of 154 patients with GC were analyzed retrospectively. Multivariate models based on regression analysis and machine learning algorithms were performed to improve the diagnostic efficacy., Results: The differentiation degree, carbohydrate antigen (CA) 199, CA724, CA242, and multiple CT findings based on LAP differed significantly between T1-3 and T4 GCs in the primary cohort (all P < 0.05). Multivariate models based on regression analysis and random forest achieved AUCs of 0.849 and 0.865 in the primary cohort, respectively., Conclusion: We developed and validated multivariate models integrating endoscopic biopsy, tumor markers, CT morphological characteristics, and CT value-related and texture parameters to predict serosal invasion in GCs and achieved favorable performance., (© 2021. The Author(s).)

Background: We aimed to analyze the differences in the peripheral blood cells and tumor biomarkers between the patients with endometriosis and healthy people, and establish a more efficient combined diagnostic model., Methods: We retrospectively analyzed the differences in the peripheral blood cells and tumor biomarkers between the patients with endometriosis and healthy people. Binary logistic regression analysis was used to establish a combined diagnostic model. We plotted the receiver operator characteristic (ROC) curve to analyze the diagnostic efficiency of different diagnostic indexes., Results: Compared with patients in the control group, patients in the endometriosis group had significantly lower eosinophil% (p = 0.045), neutrophil (p = 0.001), lymphocyte (p < 0.001), red blood cells (RBCs) (p < 0.001), and hemoglobin (HGB) (p < 0.001), and had significantly higher monocyte% (p = 0.008), monocyte-to-lymphocyte ratio (MLR) (p = 0.001), platelet-to-lymphocyte ratio (PLR) (p < 0.001), carbohydrate antigen (CA)-199 (p < 0.001), CA125 (p < 0.001), human epididymis protein (HE)-4 (p < 0.001), and the risk of ovarian malignancy algorithm (ROMA) (p < 0.001). The combined diagnostic model of HGB, CA199, CA125, and HE4 was established by binary logistic regression analysis. The ROC curve showed that the combined diagnostic model reached a sensitivity of 85.4%, a specificity of 78.83%, and an area under the curve of 0.900, which was significantly higher than that of the individual index in endometriosis diagnosis., Conclusion: The combined diagnostic model of HGB, CA199, CA125, and HE4 may provide a new approach for the early non-invasive diagnosis of endometriosis., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)