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Glioblastoma is a highly aggressive neoplasm and the most common primary malignant brain tumor. Endothelial tissue plays a critical role in glioblastoma growth and progression, facilitating angiogenesis, cellular communication, and tumorigenesis. In this review, we present an up-to-date and comprehensive summary of the role of endothelial cells in glioblastomas, along with an overview of recent developments in glioblastoma therapies and tumor endothelial marker identification.

Current research is focused on utilizing EVs as a biopsy tool to improve the diagnostic accuracy of HCC, reduce surgical risk, and explore their potential in modulating drug resistance and advancing immunotherapeutic strategies. Extracellular vesicles (EVs) have been increasingly recognized as important non-invasive biomarkers in hepatocellular carcinoma (HCC) due to the presence of a variety of biomolecules within them, such as proteins and RNAs, etc. EVs play a key role in the early detection, diagnosis, treatment, and prognostic monitoring of HCC. These vesicles influence the development of HCC and therapeutic response in a variety of ways, including influencing the tumor microenvironment, modulating drug resistance, and participating in immune regulatory mechanisms. In addition, specific molecules such as miRNAs and specific proteins in EVs are regarded as potential markers for monitoring treatment response and recurrence of HCC, which have certain research space and development prospects. In this paper, we summarize the aspects of EVs as HCC diagnostic and drug resistance markers, and also discuss the questions that may be faced in the development of EVs as markers. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial cancer is an important problem and is among the leading causes of reproductive system cancer in women. Every year, the number of cases of the disease only increases, and a high mortality rate from this disease is also recorded. The risk stratification of patients with endometrial carcinoma is based on the severity of the oncological process progression, which makes it necessary to study new diagnostic methods for the more accurate determination of lymph node involvement. Currently, new medical–genetic factors, which may be relevant for assessing the risk of metastasis and disease progression, are actively being studied. Candidate genes, microRNA, and other various biomarkers are being studied, promising the benefit of choosing more effective treatments. Background: According to epidemiological studies, endometrial carcinoma is one of the most frequently diagnosed malignancies of the female reproductive system, with an increasing incidence. Currently, the risk stratification of this neoplasm takes into account the stage, degree of tumor differentiation, histological type and depth of myometrial invasion. Since the publication of the last International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer in 2009, numerous reports have appeared on the molecular characteristics of different types of endometrial carcinoma. Taking this into account, the FIGO Committee determined in 2023 that changes and updates to the staging system are justified to reflect new information about this tumor. Due to the high prevalence of the disease and mortality from endometrial cancer, an in-depth study of the molecular genetic characteristics of tumor cells is relevant; the results of such studies can be used to improve the efficiency of diagnosis, assess the risk of metastasis and prognosis of the disease. Lymph node assessment is crucial for the choice of treatment strategy for endometrial cancer, since metastatic lymph node involvement is one of the main factors affecting prognosis. At the same time, the criteria for the appropriateness of lymphadenectomy in low-differentiated malignant tumors are not clearly defined. Various molecular methods have been proposed to assess the status of lymph nodes; candidate genes are being studied as potential diagnostic biomarkers, as well as microRNA. The aim of the study was to analyze the literature data on numerous studies of molecular risk factors for progression in endometrioid carcinoma, as well as to preserve the most important marker changes in relation to the prognostic development of this disease. Methods: A literature review was conducted using data from the electronic databases PubMed, Google Scholar, and Wiley Cochrane Library for the period from 2018 to 2023 using the specific keywords. Results: The current scientific genetic studies on metastasis and prognostic factors in uterine cancer were analyzed, and a systematization of the reviewed data from the modern literature was done. Conclusions: To select the most effective treatment - intraoperative, adjuvant or combination therapy, minimize postoperative risks of lymphadenectomy and clearly predict the results - further study of the molecular genetic features of endometrial cancer is necessary. [ABSTRACT FROM AUTHOR]

Purpose: Macrophage migration inhibitory factor (MIF) is an integral cytokine for the modulation of both innate and adaptive immunity and is involved in the pathogenesis of various cancers. However, conflicting findings on the relationship between MIF polymorphisms and breast cancer (BC) have been reported in earlier research. We investigated the clinical value of serum MIF levels and the association between MIF rs1049829 and rs755622 variants with their serum levels and propensity to develop BC. Methods: A total of 133 treatment-naïve Egyptian BC females and 126 apparently healthy controls were matriculated in this case–control study. The serum MIF protein levels were quantified by ELISA, whereas the genotyping was executed utilizing the TaqMan® allelic discrimination assay. Results: A significant increase in the serum MIF level in BC cases was observed in comparison to control subjects (P < 0.0001), with a diagnostic potential to discriminate BC with 92.5% sensitivity and 73.7% specificity at a cut-off value > 9.47 ng/mL. Besides, a significant difference in serum MIF level was observed in BC cases with progesterone receptor (PR) negativity compared to those with PR positivity (P = 0.046). Moreover, a significant association was depicted between the rs1049829 variant of MIF gene and the protective effect against BC meanwhile the rs755622 variant demonstrated no significant link with BC risk. Conclusions: This study revealed that serum MIF levels may be regarded as a promising serum tumor marker for BC. Also, the rs1049829 variant of the MIF gene is considered a protective candidate against BC. [ABSTRACT FROM AUTHOR]

Exosomes are critical tumor biomarkers, which can be detected by label‐free sensing of plasmonic metasurfaces with expensive antibody functionalization. Due to their low cost and small size, aptamers should be promising to replace antibodies in plasmonic metasensing of exosomes. However, research on aptamer‐based plasmonic metasensing of exosomes is still unexplored. Here, the optical near‐field sensing mechanism of aptamer‐based plasmonic metasurface (APM) is investigated. Based on the study of the evanescent field of APM, using thiol‐modified aptamer boosts the utilization rate of resonance wavelength shift from 27.5% to 83.3% compared to biotinylated aptamers, attributed to a significant reduction in the near‐field occupation of the biofunction layer. Moreover, APM biosensors effectively detect clinical serum exosomes for breast cancer (BC) diagnosis and classification. The receiver operating characteristic analysis shows an area under the curve of 99.3% for APM diagnosis, surpassing the 79.1% for hematological tests of the conventional BC biomarker CA153. The results also indicate that APM biosensors can be a noninvasive tool for molecular classification of BC with great distinguishment of P < 0.0001. The research demonstrates that APM biosensors are enabling a reliable and convenient platform to facilitate clinical hematological tests of exosomes for auxiliary diagnosis of cancer. [ABSTRACT FROM AUTHOR]

To establish age- and sex-specific reference intervals (RIs) for serum tumor markers (AFP, CEA, CA125, CA199, CA153, HE4, CA724, CYFRA21-1, PSA, and NSE) among a cohort of healthy individuals in South China, a retrospective analysis was conducted on 51,353 samples collected from 2015 to 2020, during health assessments at Guangdong Provincial People's Hospital. The influence of age and gender on serum tumor markers was investigated. New RIs were determined using non-parametric rank-based methods per CLSI EP28-A3C guidelines. Significant differences were detected across age groups for AFP, CEA, CA125, CA199, HE4, CYFRA21-1, PSA, and NSE (p < 0.05). The upper reference limits (URLs) for CA153 and HE4 are significantly lower compared to our current laboratory standards. The URL for CA125 exceeds these limits in individuals under 50 but decreases in those aged 50 and above. For CA199, CEA, and PSA, the URLs are below current standards in individuals younger than 60 but exceed them in those aged 60 and older. Noteworthy elevations were observed in CA724, CYFRA21-1, and NSE levels. Our study establishes age- and sex-specific RIs for ten serum tumor markers among healthy individuals from South China, providing a fundamental resource for the prevention, early detection, and management of tumor-related disorders. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical effects of intraperitoneal chemohyperthermia (IPCH) in the treatment of postoperative patients with advanced stage ovarian cancer, and its impacts on tumor markers and immune functions. Methods: This is a retrospective study. One hundred and twenty patients with advanced stage ovarian cancer received in Shanghai 7th People’s Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from May 10, 2022 to June 10, 2023 were selected and randomly divided into control and study groups (n=60 each group). Patients in the control group were administered routine intravenous chemotherapy, the study group underwent IPCH besides routine intravenous chemotherapy based on the control group. Comparatively analyzed the clinical effects, adverse reaction occurrence rates, and variations in relevant observation targets, the tumor marker after and before the treatment. Results: Total efficacy in the study and control groups are proved to be with statistically significant differences. The occurrence of adverse reactions proved that no significant differences is seen between both groups. After the treatment, CEA, CA19-9, and CA125 levels in patients of the study group are apparently lower than those in the control group, showing statistically significant differences; expression levels of CD3+, CD4+ and CD4+/CD8+, in the study group were enormously above those in the control group after the treatment, with statistically significant differences. Conclusions: IPCH has the potential to effectively enhance comprehensively clinical therapeutic effects among postoperative patients with ovarian cancer, significantly improve patients’ immune states, and evidently reduce expression levels of various tumor markers. [ABSTRACT FROM AUTHOR]

Introduction: Anti-p53 antibody (p53Ab) is useful for monitoring colorectal cancer (CRC) recurrence. We retrospectively analyzed the clinical impact of p53Ab ratio (p53R) before and after surgery to predict recurrence in patients with CRC. Methods: In total, 1,223 patients with stage I–III CRC who underwent curative surgery between January 2005 and December 2019 were enrolled in this retrospective study. In patients with elevated p53Ab levels, p53R was calculated by measuring p53Ab levels within 1 month preoperatively and 3 months postoperatively. The optimal p53R level was determined, and its relationship with clinicopathological factors and prognosis was examined. We also evaluated the efficacy of the combination of p53R and preoperative carcinoembryonic antigen (CEA) values. Results: Overall, 341 patients (27.9%) showed elevated p53Ab levels. Preoperative p53Ab levels were significantly associated with tumor location, lymphatic invasion, and venous invasion. The p53R level was significantly higher in patients with recurrent disease. Patients with high p53R levels had significantly shorter relapse-free survival than those with low p53R levels (p < 0.001). When p53R was combined with preoperative CEA values, specificity improved to 0.97, with an accuracy of 0.88. Conclusion: In patients with CRC and elevated preoperative p53Ab levels, p53R expression may be prognostically useful after radical resection. Furthermore, the combination of p53R and preoperative CEA levels may be useful for postoperative follow-ups. [ABSTRACT FROM AUTHOR]

Copyright of Baghdad Science Journal is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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. [ABSTRACT FROM AUTHOR]

CA 15-3 and CEA are tumor markers used in routine clinical care for breast cancer and colorectal cancer, among others. Current measurement procedures (MP) for these tumor markers are considered to be insufficiently harmonized. This study investigated the achievable harmonization for CA 15-3 and CEA by using an in silico simulation of external quality assessment (EQA) data from multiple EQA programs using patient-pool based samples.CA 15-3 and CEA data from SKML (2021), UK NEQAS (2020–2021) and KEQAS (2020–2021) were used. A harmonization protocol was defined in which MPs that were considered equivalent were used to value assign EQA samples, and recalibration was only required if the MP had a bias of >5 % with value assigned EQA. Harmonization status was assessed by determining the mean level of agreement and residual variation by CV (%).Only MPs from Abbott, Beckman, Roche and Siemens were available in all EQA programs. For CA 15-3, recalibration was proposed for Beckman MP only and for CEA, recalibration was proposed for Siemens MP only. When the harmonization procedures were applied, for CA 15-3 the pre-harmonization mean bias range per MP was reduced from −29.28 to 9.86 %, into −0.09–0.12 % after harmonization. For CEA, the mean bias range per MP was reduced from −23.78 to 2.00 % pre-harmonization to −3.13–1.42 % post-harmonization.The present study suggests that a significant improvement in the harmonization status of CA 15-3 and CEA may be achieved by recalibration of a limited number of MPs. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma (CCA) is a malignant neoplasm originating from biliary epithelial cells. During the early stage, the patients do not show any symptoms, leading to wide and extensive spread of this disease. Nowadays, there has not been a single serum tumor marker which can be used for effective screening of the disease or classification of the patients. This study therefore aims to determine an appropriate serum marker for screening of the patients with early staged CCA by using a technique of data mining. Beginning with the C4.5 Decision tree and Logistic Regression for selection of serum markers for effective screening of the patients with CCA, the selected markers were then used for classification of the patients with CCA from non-CCA patients, and CCA from Benign Biliary Disease (BBD) by C4.5 Decision tree, Logistic Regression, Random Forest, and Artificial Neural Network. In this work, seven serum tumor markers were used, including Carbohydrate Antigen 125 (CA125), Carbohydrate Antigens 19-9 (CA19-9), Carbohydrate Antigen 242 (CA242), Carbohydrate Antigen 50 (CA50), Carbohydrate Antigen 72-4 (CA72-4), Carcinoembryonic Antigen (CEA), Cy-tokeratin-19Fragment (CYFRA 21-1). The model was used to classify the CCA and non-CCA patients and it was discovered that the serum tumor markers which could most efficiently classify the CCA patients from the non-CCA patients were the combination of CA125 and CA242 suggested by the Logistic Regression with C4.5 Decision tree as the classifier, yielding the best performance, with Sensitivity and Specificity being 75.88 % and 86.82%, respectively. In contrast, the classification of CCA patients from BBD patients was best performed by the serum tumor markers CA125 and CA72-4 suggested by C4.5 Decision tree with Logistic Regression or Random Forest as the classifier. [ABSTRACT FROM AUTHOR]

Background: Insulinoma is a neuroendocrine tumor (NET), with its main clinical manifestation being the hypoglycemic syndrome. The symptoms of hypoglycemia are nonspecific, and therefore, in most cases, the diagnosis is made untimely. The Russian clinical guidelines for the diagnosis and treatment of NET suggest as a diagnostic test that the universal circulating marker of all NET, chromogranin A (CgA) be determined. However, the literature data on the sensitivity of CgA in the diagnosis of insulinoma are contradictory. Aim: To evaluate the diagnostic effectiveness of the CgA test in the diagnosis of insulinoma. Materials and methods: This was a hospital-based single-center, cross-sectional comparative (first step) and prospective non-comparative (second step) study conducted from 2016 to 2022. During the first part of the study, we determined serum CgA in 120 patients with suspected non-diabetic hypoglycemia and compared its levels in the patients with and without confirmed insulinoma (n = 87 and n = 33, respectively). During the second study step, CgA was measured in the insulinoma patients at 6 [4.0; 7.0] months after surgery. The CgA levels at baseline and post-surgery were analyzed in 74 patients (those with recurring non-diabetic hypoglycemia were excluded from the analysis). Results: In the study subjects without insulinoma, the median CgA level was 0.7 [0.5; 1.1] (range, 0.1 to 2.0) nmol/l and the difference (with Bonferroni adjustment) from its levels in the patients with insulinoma before surgery was non-significant (1.0 [0.7; 1.4], range, 0.1 to 8.5 nmol/l, р = 0.045). The CgA concentration in the insulinoma patients after surgery was 0.9 [0.7; 1.2], range, 0 to 1.9 nmol/l and significantly differed from that at baseline (1.0 [0.7; 1.4], range, 0.1 to 8.5 nmol/l, p = 0.012, Wilcoxon test). In the patients with insulinoma before surgery the CgA levels exceeding the generally accepted reference range ( 2 nmol/l) was found in 11.5% (n = 10), with its median level of 2.5 [2.3; 4.1], range 2.3 to 8.5 nmol/l. There were no significant associations between the CgA levels and localization, tumor numbers, their size and malignization grade, insulin and proinsulin values, and duration of fasting. The sensitivity and specificity of the CgA test were 12% [95% confidence interval [CI]: 6%–20%] and 100% [95% CI: 97%–100%], respectively. The prognostic value of a positive result (PVPR) was 100% [95% CI: 69%–100%] and the prognostic value of a negative result (PVNR) 30% [95% CI: 28%–32%]. Conclusion: As a diagnostic test, CgA has high specificity and prognostic value of a positive result. However, the uncertainty of the prognostic value of a negative result is unacceptably high. A special study is required to clarify the operational characteristics of CgA in insulinoma.

Background: Breast cancer constitutes a significant proportion of malignancies among the female population, accounting for approximately 25% of all cancer cases on a global scale. Human epidermal growth factor receptor-2 (HER2) is the more reliable marker in breast cancer diagnosis. Objective: This study investigates the potential of soluble salivary HER2 in breast cancer diagnosis and explores its correlation with demographic and hormonal factors. Materials and Methods: A total of 45 subjects were selected and divided into three groups: Group A: healthy patients (n = 15), Group B: HER2-negative breast cancer patients (n = 15), and Group C: HER2-positive breast cancer patients (n = 15). Patients’ saliva was collected, and assessment of salivary soluble HER2 was performed by using an enzyme-linked immunosorbent assay kit. Results: Salivary HER2 levels were 32.3 pg/ml in healthy group, 43.2 pg/ml in HER2-negative group, and 147.8 pg/ml in HER2-positive group. On evaluating the risk factors associated with the salivary HER2 levels, increased age (P = 0.007), positive family history (P = 0.006), patients with the habit of tobacco chewing (P = 0.001), and patients with no breastfeeding history (P = 0.001) showed a statistically significant result. Conclusion: Salivary HER2 levels were higher in both HER2-positive and -negative breast cancer groups compared to controls, indicating its potential as a noninvasive diagnostic tool for breast cancer screening.

Abstract Background Independent and valid prognostic predictors for locally advanced gastric cancer (LAGC) patients with non-elevated serum tumor markers (Triple-negative: CA199

Background: Ovarian endometriosis cysts (OEC) are common chronic diseases occurring in women of reproductive age. Hormone therapy, including the use of oral contraceptives (COCs) and progestins, is widely employed in the treatment of endometriosis and OEC. Objective: This study aims to compare therapeutic effects of long-term daily use of dienogest (DNG, 2 mg) versus drospirenone (DRSP, 3 mg)/ethinyl estradiol (EE, 20 μg) daily on ovarian endometrial cysts, particularly focusing on cysts suppression. Methods: A retrospective analysis was conducted on 84 patients diagnosed with OEC, with 42 receiving DNG and 42 treated with DRSP/EE. After 6 months, assessments were made regarding pain symptoms, size of OEC, tumor markers, and adverse reactions. Results: After 6 months of treatment, both DNG and DRSP/EE effectively alleviated pain in patients with ovarian endometriotic cysts. DNG demonstrated more significant improvements than DRSP/EE in reducing tumor size, mainly in terms of higher drug efficacy and greater percentage of tumor shrinkage. However, DRSP/EE significantly reduced the expression of the tumor markers CA125 and CA199 in our study. Patients taking DNG had a higher likelihood of experiencing side effects than those on DRSP/EE, mainly vaginal bleeding and irregular menstrual periods. Conclusions: Both DNG and DRSP/EE are effective in treating ovarian endometrial cysts. DNG appears to be superior in terms of tumor reduction, while DRSP/EE more significantly decreases the expression of the tumor markers and has fewer side effects. [ABSTRACT FROM AUTHOR]

Yuexi Liu,&ast; Qiuying Gu,&ast; Yao Xiao, Xing Wei, Jinlong Wang, Xiaolan Huang, Hua Linghu Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Linghu, Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Email linghuhua@cqmu.edu.cnPurpose: To evaluate Ki67 expression and prognostic value during neoadjuvant chemotherapy (NACT) in advanced epithelial ovarian cancer (EOC).Patients and Methods: 95 patients with advanced EOC receiving NACT followed by interval debulking surgery (IDS) were available for tissue samples from matched pre- and post-therapy specimens. The expression of Ki-67 was evaluated by immunohistochemistry and classified by percentage of stained cells. The optimal cutoff values of the Ki67 were assessed by receiver operating characteristic analysis. Kaplan-Meier analysis, the Log rank test, and Cox regression analysis were carried out to analyze survival.Results: Post-NACT Ki67 was an independent prognostic factor for recurrence by univariate (HR: 1.8, 95% CI: 1.1– 3.0, P-value: 0.023) and multivariate (HR: 1.88, 95% CI: 1.08– 3.26, P-value: 0.025) analysis. Residual disease > 1cm (HR: 2.69, 95% CI: 1.31– 5.54, P-value: 0.0070) and pre-treatment CA125 ≥ 1432 U/mL (HR: 2.00, 95% CI: 1.13– 3.55, P-value: 0.017) were also independent risk factors for progression-free survival (PFS) in multivariate analysis. Post-NACT Ki67 ≥ 20% was an independent risk factor for PFS, however, baseline Ki67 and Ki67 change did not suggest prognostic significance. In patients with high CA125, the median PFS for patients with high postKi67 (median PFS: 15.0 months, 95% CI: 13.4– 16.6 months) was significantly (P-value: 0.013) poorer compared to patients with low postKi67 (median PFS: 30.0 months, 95% CI: 13.5– 46.5 months).Conclusion: Post-NACT Ki67 ≥ 20% was an independent factor associated with poorer PFS in patients with advanced-stage EOC undergoing NACT followed by IDS. The combination of post-NACT Ki67 and pretreatment CA125 could better identify patients with poorer PFS in NACT-administered patients.Keywords: interval debulking surgery, progression-free survival, overall survival, tumor marker

Introduction. Local hypermethylation of gene promoters and global genome hypomethylation are well-known manifestations of aberrant methylation associated with carcinogenesis. We investigated this phenomenon as a possible diagnostic marker for liquid biopsy of colorectal cancer using the original quantitative DNA melting analysis with hybridiza-tion probes (qDMA-HP) method. Aim. To quantify the methylation of HIST1H4F promoter and LINE-1 transposon in circulating blood plasma DNA of colorectal cancer patients. Materials and methods. Bisulfite-treated DNA samples isolated from blood plasma of healthy donors and cancer patients were analyzed. HIST1H4F methylation was assessed by asymmetric polymerase chain reaction with hybridized probe and post-amplification melting of probe / amplicon hybrids. To test for repetitive and highly polymorphic LINE-1 sequences, asymmetric polymerase chain reaction with hybridized probe and SYBR Green intercalating dye was used, followed by melting of hybrids and analysis of multicomponent melt curves. Results. High diagnostic efficiency of LINE-1 and HIST1H4F methylation markers in liquid biopsy of colorectal cancer was demonstrated with the area under the ROC curve = 0.92, sensitivity – 100 %, specificity – 84 %. Cross validation supports this result. Hypermethylation of HIST1H4F and hypomethylation of LINE-1 are statistically significantly correlated (Spearman correlation coefficient r = 0.4; p = 0.01). Conclusion. The qDMA-HP is suitable for quantitative assessment of aberrant methylation of various clinically significant genes.

Serum and pleural fluid tumor markers are well-recognized auxiliary diagnostic tools for malignant pleural effusion (MPE). Here, we discuss some pearls and pitfalls regarding the role of tumor markers in MPE management. The following issues are discussed in this article: What is the appropriate clinical scenario for evaluating pleural tumor markers? Which tumor markers should be advocated for diagnosing MPE? Can extremely high levels of tumor markers be employed to establish a diagnosis of MPE? Does the serum-to-pleural fluid ratio of a tumor marker have the same diagnostic efficacy as the measurement of that marker alone in the pleural fluid? Can tumor markers be used to estimate the risk of specific cancers? What should be considered when interpreting the diagnostic accuracy of tumor markers? How should tumor marker studies be performed? We addressed these issues with published works, particularly systematic reviews and meta-analyses. [ABSTRACT FROM AUTHOR]

Tumor markers such as carbohydrate antigen 19-9 (CA19-9) are generally useful in ruling out malignancy of hepatic cysts. The patient was a 72-year-old man who had a ruptured liver cyst in the right liver, which had been noted since he was 67 years old at another hospital. The initial laboratory tests demonstrated elevated CA19-9 (193 784.3 U/mL). We made the diagnosis with a simple ruptured liver cyst from magnetic resonance imaging and cytological examination of ascites, and laparoscopic fenestration with drainage of the abdominal fluid was performed. Pathological diagnosis of the resected wall cyst was non-parasitic simple hepatic cyst with acute inflammation and hemorrhage. The patient's serum levels of CA19-9 were 164.0 U/mL on postoperative day 23. The follow-up abdominal computed tomography scan performed 2 months later did not any finding of tumor. [ABSTRACT FROM AUTHOR]

A highly sensitive surface-enhanced Raman scattering (SERS) biosensor has been developed for the detection of microRNA-21 (miR-21) using an isothermal enzyme-free cascade amplification method involving catalytic hairpin assembly (CHA) and hybridization chain reaction (HCR). The CHA reaction is triggered by the target miR-21, which causes hairpin DNA (C1 and C2) to self-assemble into CHA products. After AgNPs@Capture captures the resulting CHA product, the HCR reaction is started, forming long-stranded DNA on the surface of AgNPs. A strong SERS signal is generated due to the presence of a large amount of the Raman reporter methylene blue (MB) in the vicinity of the SERS "hot spot" on the surface of AgNPs. The monitoring of the SERS signal changes of MB allows for the highly sensitive and specific detection of miR-21. In optimal conditions, the biosensor exhibits a satisfactory linear range and a low detection limit for miR-21 of 42.3 fM. Additionally, this SERS biosensor shows outstanding selectivity and reproducibility. The application of this methodology to clinical blood samples allows for the differentiation of cancer patients from healthy controls. As a result, the CHA-HCR amplification strategy used in this SERS biosensor could be a useful tool for miRNA detection and early cancer screening. [ABSTRACT FROM AUTHOR]

Copyright of Journal of China Medical University is the property of Journal of China Medical University Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Sensitive detection of tumor markers is one of the most important safeguards for early diagnosis of cancer, selection of therapeutic strategies and prognostic monitoring. The content of tumor markers in serum is low, usually existing at trace level, and even very few other tumor markers are only on the order of femtograms or picograms per millilitre of serum, and subtle changes in their concentrations are indicative of tumor occurrence, progression and therapeutic efficacy. It is of great clinical significance and has received extensive attention how to achieve sensitive detection of small concentration changes of tumor markers at trace level. Because of its high sensitivity, fast response, easy operation, and miniaturization of the instrument, electrochemical immunosensors have received much attention and made great progress in the study of detecting small concentration changes of tumor markers at trace level. This paper reviews the progress made in catalytic reactions to enhance the performance of electrochemical detection of tumor markers, with special focus on the application of bioenzymes, nano-enzymes, and the use of electrochemical metal catalysts, and also provides an outlook on the problems to be solved. [ABSTRACT FROM AUTHOR]

• To examine the effect of factors on HE4 values in a national representative sample of women in the United States. • Elevated HE4 levels were associated with postmenopausal status, endometriosis, nicotine exposure, and poor renal function. • Decreased HE4 levels was associated with use of oral contraceptives. • This study of samples from 98.5 million non-institutionalized women in the United States confirms variables that affect HE4 levels. Human epididymis protein 4 (HE4) is a tumor marker overexpressed in ovarian cancer and is commonly utilized to aid with diagnosis of an adnexal mass. HE4 levels vary based on pregnancy, age, menopausal status, and tobacco use. The objective of this study was to evaluate population-based data to examine factors that affect HE4 among adult women in the United States and stratify levels of HE4 by demographic and gynecologic factors. A retrospective analysis was conducted using data from 2,480 women aged 20 + who participated in the National Health and Nutrition Examination Survey (2001–2002). From these cross-sectional data, serum HE4 and cotinine, a marker of tobacco exposure, were combined with demographic and interview data. Estimated glomerular filtration rates (eGFR) were based on serum creatinine, age, sex, and race. Other variables of interest included menopausal status, pregnancy, and various gynecologic factors. Summary HE4 data are provided as geometric means with associated 95 % confidence intervals. HE4 levels were independently associated with age, renal function, and nicotine use, all p < 0.001. Pre-menopausal women with a history of endometriosis were found to have elevated HE4 levels compared to those without, p < 0.01; however, we found no such difference among post-menopausal women. Adjusting for age, no differences in HE4 were found based on race/ethnicity, p = 0.29. HE4 levels showed statistically significant associations with income level; however, these were small and clinically irrelevant. This study provides evaluation of HE4 levels among a data set representative of 98.5 million non-institutionalized women in the United States and gives insight into extraneous factors that may influence these levels. [ABSTRACT FROM AUTHOR]

Introduction: Previously we demonstrated that elevated serum CYFRA 21 − 1 is a reliable diagnostic and prognostic biomarker for biliary tract cancers. This study aims to explore the diagnostic performance of bile CYFRA 21 − 1 (bCYFRA 21 − 1) in discriminating malignant biliary obstruction (MBO) caused by cholangiocarcinoma (CCA). Methods: 77 CCA patients ((17 intrahepatic CCA (iCCA), 49 perihilar CCA (pCCA) and 11 distal CCA (dCCA)) and 43 benign patients with biliary obstruction were enrolled. Serum and bile levels of CYFRA 21 − 1, carcinoembryonic antigen (CEA) and carbohydrate antigen 19 − 9 (CA19-9) were quantified. Diagnostic performances of these biomarkers were estimated by receiver operator characteristic curves. Subgroups analysis of these tumor markers among CCA subtypes was performed. Results: High bCYFRA 21 − 1 (cut-off value of 59.25 ng/mL with sensitivity of 0.889 and specificity of 0.750) and high bile to serum ratio of CYFRA 21 − 1 (b/sCYFRA 21 − 1, cut-off value of 31.55 with sensitivity of 0.741 and specificity of 0.778) achieved better diagnostic performance than any other biomarker in discriminating MBO. Subgroup analysis revealed that bCYFRA 21 − 1 was significantly elevated in all CCA subtypes; moreover b/sCYFRA 21 − 1 was upregulated in pCCA and dCCA (the mean b/sCYFRA 21 − 1 of pCCA was highest among CCA subtypes: 57.90, IQR 29.82-112.27). Conclusions: Both high biliary CYFRA 21 − 1 and high bile to serum ratio of CYFRA 21 − 1 were reliable diagnostic biomarkers for MBO caused by CCA. [ABSTRACT FROM AUTHOR]

Current research is focused on utilizing EVs as a biopsy tool to improve the diagnostic accuracy of HCC, reduce surgical risk, and explore their potential in modulating drug resistance and advancing immunotherapeutic strategies. Extracellular vesicles (EVs) have been increasingly recognized as important non-invasive biomarkers in hepatocellular carcinoma (HCC) due to the presence of a variety of biomolecules within them, such as proteins and RNAs, etc. EVs play a key role in the early detection, diagnosis, treatment, and prognostic monitoring of HCC. These vesicles influence the development of HCC and therapeutic response in a variety of ways, including influencing the tumor microenvironment, modulating drug resistance, and participating in immune regulatory mechanisms. In addition, specific molecules such as miRNAs and specific proteins in EVs are regarded as potential markers for monitoring treatment response and recurrence of HCC, which have certain research space and development prospects. In this paper, we summarize the aspects of EVs as HCC diagnostic and drug resistance markers, and also discuss the questions that may be faced in the development of EVs as markers.

Sclerosing stromal tumors are a rare type of ovarian tumor in the category of sex cord stromal tumors, which arise from the ovarian connective tissue. This report concerns a case of a sclerosing stromal tumor in a 19-year-old nulliparous woman who presented with the chief complaints of menstrual irregularities and dyspareunia. Preoperative imaging revealed a complex right adnexal mass with blood flow and without associated ascites. Tumor markers were all normal except lactate dehydrogenase, which was elevated. The elevated lactate dehydrogenase, in combination with patient age and menstrual irregularities, initially misdirected the clinicians toward suspicion for dysgerminoma or other malignant germ cell tumor of the ovary. Clinicians should beware of excluding the diagnosis of sex cord stromal tumor on the differential in a young person with an adnexal mass and elevated lactate dehydrogenase.

Objective: To observe the clinical efficacy of xindili monoclonal antibody injection combined with S-1 and oxaliplatin (SOX) regimen as neoadjuvant therapy for locally advanced gastric cancer. Methods: According to the random number table method, 98 patients with locally advanced gastric cancer received in Xuzhou Cancer Hospital from January 2022 to June 2023 were divided into control group (49 cases treated with SOX regimen) and study group (49 cases treated with xindili monoclonal antibody injection on the basis of control group). The efficacy [objective response rate (ORR), disease control rate (DCR)], serum tumor marker levels, T lymphocyte subsets and incidence of adverse reactions were compared between two groups. Results: In study group, the ORR and DCR were higher than those in control group (P<0.05). After treatment, CEA, CA724, CA125 and CD8+ in study group were lower than those in control group, CD4+ and CD4+/CD8+ were higher than those in control group(P<0.05). The incidence of adverse reactions in the study group was 32.65% higher than that in the control group, which was 28.57%, but there was no difference between the two groups (P>0.05). Conclusion: Xindili monoclonal antibody injection combined with SOX regimen neoadjuvant therapy for locally advanced gastric cancer, which can effectively prevent disease progression, reduce serum tumor marker levels, improve immune function. [ABSTRACT FROM AUTHOR]

Abstract Background The aim is to establish and verify reference intervals (RIs) for serum tumor markers for an apparently healthy elderly population in Southwestern China using an indirect method. Methods Data from 35,635 apparently healthy elderly individuals aged 60 years and above were obtained in West China Hospital from April 2020 to December 2021. We utilized the Box-Cox conversion combined with the Tukey method to normalize the data and eliminate outliers. Subgroups are divided according to gender and age to examine the division of RIs. The Z-test was used to compare differences between groups, and 95% distribution RIs were calculated using a nonparametric method. Results In the study, we observed that the RIs for serum ferritin and Des-γ-carboxy prothrombin (DCP) were wider for men, ranging from 64.18 to 865.80 ng/ml and 14.00 to 33.00 mAU/ml, respectively, compared to women, whose ranges were 52.58 to 585.88 ng/ml and 13.00 to 29.00 mAU/ml. For other biomarkers, the overall RIs were established as follows: alpha-fetoprotein (AFP) 0–6.75 ng/ml, carcinoembryonic antigen (CEA) 0–4.85 ng/ml, carbohydrate antigen15-3 (CA15-3) for females 0–22.00 U/ml, carbohydrate antigen19-9 (CA19-9) 0–28.10 U/ml, carbohydrate antigen125 (CA125) 0–20.96 U/ml, cytokeratin 19 fragment (CYFRA21-1) 0–4.66 U/ml, neuron-specific enolase (NSE) 0–19.41 ng/ml, total and free prostate-specific antigens (tPSA and fPSA) for males 0–5.26 ng/ml and 0–1.09 ng/ml. The RIs for all these biomarkers have been validated through our rigorous processes. Conclusion This study preliminarily established 95% RIs for an apparently healthy elderly population in Southwestern China. Using real-world data and an indirect method, simple and reliable RIs for an elderly population can be both established and verified, which are suitable for application in various clinical laboratories.

Abstract Purpose To explore the clinical value of tumor abnormal protein (TAP) in the diagnosis and prognosis evaluation of prostate cancer. Methods This study enrolled a total of 265 patients who underwent prostate biopsy procedures from December 2017. TAP levels were assayed in their blood samples using a validated TAP testing kit. Comprehensive pathological assessments, including Gleason scores, TNM staging, and AJCC prognosis stages, were conducted on prostate cancer patients. Further analysis was carried out to examine the correlation between TAP expression levels and various clinical characteristics. Results A significantly elevated TAP concentration was discerned in prostate cancer patients relative to those with benign prostate hyperplasia. Moreover, a significantly elevated TAP expression was detected in prostate cancer patients with high Gleason score (≥ 8) and advanced stages (III and IV), as compared to those with Gleason scores of 6 and 7 and lower stages (I and II). When diagnosing prostate cancer in gray area of PSA, TAP demonstrated superior diagnostic capabilities over PSA alone, with higher diagnostic sensitivity, specificity and accuracy than fPSA/tPSA ratio. Additionally, post-surgical or hormonal treatment, there was a marked reduction in TAP expression level among prostate cancer patients. Conclusion The assessment of TAP presents itself as a promising tool for early diagnosis and holds potential for sensitivity in monitoring treatment reponse in prostate cancer patients.

Abstract Matrix metalloproteinases (MMPs) had a variety of subtypes, which may be related to tumor invasion and angiogenesis, and the polymorphisms from MMPs have been also associated with the susceptibility to a variety of tumors, including prostate cancer (PCa). However, previous studies have not systematically analyzed the association between MMP and prostate cancer, so we conducted systematic data collection and analyzed to evaluate the relationship among polymorphisms in MMPs and PCa susceptibility. We searched PubMed, Web of Science, Embase and Google Scholar for all papers published up to Apr 3rd, 2023, and systematically analyzed the relationship among MMP1-1607 2G/1G, MMP2-1306 T/C, MMP2-735 T/C, MMP7-181 G/A, MMP9-1562 T/C and PCa susceptibility using multiple comparative models and subgroup analyses. We found that MMP2-1306 T/C polymorphism showed associations with PCa susceptibility, with the Ethnicity subgroup (Asian) being more pronounced. Similarly, MMP9-1562 T/C has also had associations with PCa susceptibility. Our current study found that the polymorphisms of, MMP2-1306 T/C, and MMP9-1562 T/C had strong associations with PCa risk.

Abstract Objectives In comparison to the subjects without diabetes, a greater concentration of serum carbohydrate antigen 19 − 9 (CA 19 − 9) was observed in the subjects with diabetes. Nevertheless, since the occurrence of abnormal CA 19 − 9 is not widespread among the whole diabetic population, this phenomenon has not attracted enough attention. The prevalence of abnormal CA 19 − 9 in hospitalized patients with diabetes was the focus of our research. Method A total of 385 subjects with diabetes and 200 controls were enrolled and all had been tested the CA19-9 levels. Cases of cancers were excluded through examination and followup for 1 year. Results We found that the rate of patients with abnormal CA19-9 level was 8.3%. The rate of patients with abnormal CA19-9 level was 14.0% in the HbA1c ≥ 9% group, and 3.0% in the HbA1c

This study aimed to investigate the efficacy of thymosin α1 combined with XELOX in improving immune function and reducing serum tumor markers in patients with colorectal cancer (CRC) after radical surgery. A total of 180 patients who underwent radical surgery for CRC were divided into two groups: an observation group (n = 94) receiving thymosin α1 in combination with XELOX and a control group (n = 86) receiving XELOX alone. Immune function, inflammatory factor levels, serum tumor markers, and quality of life were assessed before and after treatment. Adverse reactions and recurrence rates were compared between the two groups in 1 and 3 years. Following therapy, there was a notable increase in the levels of CD3+, CD4+, and CD4+/CD8+ in all cohorts, particularly in the observation cohort, when compared to pre-therapy levels. Conversely, CD8+ levels decreased across all cohorts, especially in the observation cohort. Additionally, there was an increase in the levels of IL-2 and IFN-γ in the observation cohort, compared to both pre-therapy and control cohort levels, while IL-6 levels decreased. The presence of CEA, CA242, and CA724 reduced significantly across all cohorts following post-therapy, particularly in the observation cohort. Post-therapy, there was a significant increase in the scoring for role, cognitive, social, emotional, and somatic functions in all cohorts, with the most significant improvement observed in the observation cohort. There were no significant differences in the incidence of side effects across cohorts, while neutropenia events were significantly lower in the observation cohort (32.98%) compared to the control cohort (48.84%). The 12-month recurrence rate showed no statistical significance across cohorts, while the observation cohort had a significantly lower three-year recurrence rate (24.47%) compared to the control cohort (59.30%). Thymosin α1 combined with XELOX is effective in improving immune function, reducing serum tumor markers, and minimizing recurrence in CRC patients after radical surgery. This combination therapy may be a promising new direction for the treatment of CRC.

Abstract Background It is difficult to predict gene mutations individually based on clinical background alone. Tumor markers may help to predict each gene mutation. Identifying tumor markers that can predict gene mutation will facilitate timely genetic testing and intervention. Methods We selected 134 cases of advanced or recurrent ALK‐positive and 172 cases of advanced or recurrent EGFR‐positive lung cancer from our clinical database. The cutoff values for the tumor markers were defined as 5.0 ng/mL or higher for carcinoembryonic antigen (CEA) and 3.5 ng/mL or higher for soluble fragment of cytokeratin 19 (CYFRA21‐1) in accordance with the institutional standards. A positive CYFRA21‐1:CEA ratio was defined as 0.7 or higher. Results The CEA‐positivity rate was 49% for ALK‐positive lung cancers and 73% for EGFR‐positive lung cancers, which was significantly different (p

Abstract Purpose The NY‐ESO‐1 antigen is highly immunogenic and often spontaneously induces an immune response in patients with cancer. We conducted a large‐scale multicenter cohort study to investigate the utility of serum NY‐ESO‐1 and p53 antibodies as predictive markers for the postoperative recurrence of gastric cancer. Here, we examined the usefulness of pre‐treatment NY‐ESO‐1 and p53 antibodies as tumor markers for the diagnosis of gastric cancer in combination with carcinoembryonic antigen (CEA) and carbohydrate antigen 19‐9 (CA19‐9). Methods A total of 1031 patients with cT3‐4 gastric cancer were enrolled in the study. NY‐ESO‐1 and p53 antibodies were assessed prior to treatment. The positivity of NY‐ESO‐1 and p53 antibodies, CEA, and CA19‐9 was evaluated before treatment. Results Serum NY‐ESO‐1 and p53 antibodies were positive in 12.6% and 18.1% of the patients, respectively. Positive NY‐ESO‐1 antibody response was correlated with male gender, higher cStage, and upper tumor location. However, a positive p53 antibody response was not associated with tumor factors. The combination of NY‐ESO‐1 or p53 antibody response with CEA and CA19‐9, or the 4‐factors, was positive in 45.1%, 49.6%, and 53.8% of patients, respectively. Moreover, the 4‐factor combination was able to detect >60% of cStage III‐IV diseases, which was 14% higher than that with the combination of CEA and CA19‐9. Conclusion The combination of NY‐ESO‐1 and p53 antibody responses to CEA and CA19‐9 increases the diagnostic accuracy of gastric cancer. Serum NY‐ESO‐1 and p53 antibodies may be useful tumor markers for gastric cancer.

This study aimed to investigate the expression and clinical significance of syncytin-1 in the serum exosomes of hepatocellular carcinoma (HCC) patients. Serum samples were collected from 61 patients with newly diagnosed HCC and 61 healthy individuals. Exosomes were extracted from serum samples and identified using transmission electron microscopy and Western blot. The relative expression levels of syncytin-1 in exosomes were determined by real-time quantitative PCR. The protein expression levels of alpha-fetoprotein and syncytin-1 in HCC patients were detected using enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed to evaluate the sensitivity and specificity of serum exosomal syncytin-1 in diagnosing HCC. The relationships between syncytin-1 expression and clinical pathological features were analyzed using receiver operating characteristic curve analysis. The results showed that the expression level of syncytin-1 in the serum of patients with newly diagnosed HCC was significantly higher than that in the normal control group (P < 0.0001). Using pathological diagnosis as the gold standard, the sensitivity and specificity of syncytin-1 for the auxiliary diagnosis of HCC were 91.3% and 75.5%, respectively, which were significantly higher than those of alpha-fetoprotein (P < 0.0001). The relative expression level of serum exosomal syncytin-1 was significantly associated with lymph node metastasis, degree of differentiation, and CNLC staging of HCC patients (P < 0.05). In conclusion, syncytin-1 in serum exosomes has high sensitivity and specificity for diagnosing HCC and can serve as a novel tumor marker for early screening, detection, and staging of HCC.

Purpose: To explore the clinical value of tumor abnormal protein (TAP) in the diagnosis and prognosis evaluation of prostate cancer. Methods: This study enrolled a total of 265 patients who underwent prostate biopsy procedures from December 2017. TAP levels were assayed in their blood samples using a validated TAP testing kit. Comprehensive pathological assessments, including Gleason scores, TNM staging, and AJCC prognosis stages, were conducted on prostate cancer patients. Further analysis was carried out to examine the correlation between TAP expression levels and various clinical characteristics. Results: A significantly elevated TAP concentration was discerned in prostate cancer patients relative to those with benign prostate hyperplasia. Moreover, a significantly elevated TAP expression was detected in prostate cancer patients with high Gleason score (≥ 8) and advanced stages (III and IV), as compared to those with Gleason scores of 6 and 7 and lower stages (I and II). When diagnosing prostate cancer in gray area of PSA, TAP demonstrated superior diagnostic capabilities over PSA alone, with higher diagnostic sensitivity, specificity and accuracy than fPSA/tPSA ratio. Additionally, post-surgical or hormonal treatment, there was a marked reduction in TAP expression level among prostate cancer patients. Conclusion: The assessment of TAP presents itself as a promising tool for early diagnosis and holds potential for sensitivity in monitoring treatment reponse in prostate cancer patients. [ABSTRACT FROM AUTHOR]

Background: The aim is to establish and verify reference intervals (RIs) for serum tumor markers for an apparently healthy elderly population in Southwestern China using an indirect method. Methods: Data from 35,635 apparently healthy elderly individuals aged 60 years and above were obtained in West China Hospital from April 2020 to December 2021. We utilized the Box-Cox conversion combined with the Tukey method to normalize the data and eliminate outliers. Subgroups are divided according to gender and age to examine the division of RIs. The Z-test was used to compare differences between groups, and 95% distribution RIs were calculated using a nonparametric method. Results: In the study, we observed that the RIs for serum ferritin and Des-γ-carboxy prothrombin (DCP) were wider for men, ranging from 64.18 to 865.80 ng/ml and 14.00 to 33.00 mAU/ml, respectively, compared to women, whose ranges were 52.58 to 585.88 ng/ml and 13.00 to 29.00 mAU/ml. For other biomarkers, the overall RIs were established as follows: alpha-fetoprotein (AFP) 0–6.75 ng/ml, carcinoembryonic antigen (CEA) 0–4.85 ng/ml, carbohydrate antigen15-3 (CA15-3) for females 0–22.00 U/ml, carbohydrate antigen19-9 (CA19-9) 0–28.10 U/ml, carbohydrate antigen125 (CA125) 0–20.96 U/ml, cytokeratin 19 fragment (CYFRA21-1) 0–4.66 U/ml, neuron-specific enolase (NSE) 0–19.41 ng/ml, total and free prostate-specific antigens (tPSA and fPSA) for males 0–5.26 ng/ml and 0–1.09 ng/ml. The RIs for all these biomarkers have been validated through our rigorous processes. Conclusion: This study preliminarily established 95% RIs for an apparently healthy elderly population in Southwestern China. Using real-world data and an indirect method, simple and reliable RIs for an elderly population can be both established and verified, which are suitable for application in various clinical laboratories. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) had a variety of subtypes, which may be related to tumor invasion and angiogenesis, and the polymorphisms from MMPs have been also associated with the susceptibility to a variety of tumors, including prostate cancer (PCa). However, previous studies have not systematically analyzed the association between MMP and prostate cancer, so we conducted systematic data collection and analyzed to evaluate the relationship among polymorphisms in MMPs and PCa susceptibility. We searched PubMed, Web of Science, Embase and Google Scholar for all papers published up to Apr 3rd, 2023, and systematically analyzed the relationship among MMP1-1607 2G/1G, MMP2-1306 T/C, MMP2-735 T/C, MMP7-181 G/A, MMP9-1562 T/C and PCa susceptibility using multiple comparative models and subgroup analyses. We found that MMP2-1306 T/C polymorphism showed associations with PCa susceptibility, with the Ethnicity subgroup (Asian) being more pronounced. Similarly, MMP9-1562 T/C has also had associations with PCa susceptibility. Our current study found that the polymorphisms of, MMP2-1306 T/C, and MMP9-1562 T/C had strong associations with PCa risk. [ABSTRACT FROM AUTHOR]

Background: Different types of inflammatory processes and fibrosis have been implicated in the pathogenesis of interstitial lung disease (ILD), a heterogeneous, diffuse, parenchymal lung disease. Acute exacerbation (AE) of ILD is characterized by significant respiratory deterioration and is associated with high mortality rates. Several serum oncomarkers have been used to determine the prognosis of ILD; however, the prognostic value of serum oncomarker levels in patients with AE-ILD remains unclear. Objective: To evaluate the prognostic value of serum oncomarker levels in patients with AE-ILD and its main subtypes. Design: Retrospective study Methods: The serum levels of 8 oncomarkers in 281 patients hospitalized with AE-ILD at our institution between 2017 and 2022 were retrospectively reviewed. The baseline characteristics and serum oncomarker levels were compared between the survival and non-survival groups of AE-ILD and its main subtypes. Multivariate logistic regression analysis was performed to identify independent prognosis-related markers, and the best prognostic predictor was analyzed using receiver operating characteristic curve (ROC) analysis. Result: Idiopathic pulmonary fibrosis (IPF; n = 65), idiopathic nonspecific interstitial pneumonia (iNSIP; n = 26), and connective tissue disease-associated interstitial lung disease (CTD-ILD; n = 161) were the three main subtypes of ILD. The in-hospital mortality rate among patients with AE-ILD was 21%. The serum oncomarker levels of most patients with AE-ILD and its main subtypes in the non-survival group were higher than those in the survival group. Multivariate analysis revealed that ferritin and cytokeratin 19 fragments (CYFRA21-1) were independent prognostic risk factors for patients hospitalized with AE-ILD or AE-CTD-ILD. CYFRA21-1 was identified as an independent prognostic risk factor for patients hospitalized with AE-IPF or AE-iNSIP. Conclusion: CYFRA21-1 may be a viable biomarker for predicting the prognosis of patients with AE-ILD, regardless of the underlying subtype of ILD. Ferritin has a prognostic value in patients with AE-ILD or AE-CTD-ILD. [ABSTRACT FROM AUTHOR]

Background: Autoantibodies targeting tumor-associated antigens (TAAbs) have emerged as promising biomarkers for early cancer detection. This research aimed to assess the diagnostic capacity of anti-BIRC5 autoantibody in detecting AFP-negative hepatocellular carcinoma (ANHCC). Methods: This research was carried out in three stages (discovery phase, validation phase, and evaluation phase) and included a total of 744 participants. Firstly, the anti-BIRC5 autoantibody was discovered using protein microarray, exhibiting a higher positive rate in ANHCC samples (ANHCCs) compared to normal control samples (NCs). Secondly, the anti-BIRC5 autoantibody was validated through enzyme-linked immunosorbent assay (ELISA) in 85 ANHCCs and 85 NCs from two clinical centers (Zhengzhou and Nanchang). Lastly, the diagnostic usefulness of the anti-BIRC5 autoantibody for hepatocellular carcinoma (HCC) was evaluated by ELISA in a cohort consisting of an additional 149 AFP-positive hepatocellular carcinoma samples (APHCCs), 95 ANHCCs and 244 NCs. The association of elevated autoantibody to high expression of BIRC5 in HCC was further explored by the database from prognosis, immune infiltration, DNA methylation, and gene mutation level. Results: In the validation phase, the area under the ROC curve (AUC) of anti-BIRC5 autoantibody to distinguish ANHCCs from NCs in Zhengzhou and Nanchang centers was 0.733 and 0.745, respectively. In the evaluation phase, the AUCs of anti-BIRC5 autoantibody for identifying ANHCCs and HCCs from NCs were 0.738 and 0.726, respectively. Furthermore, when combined with AFP, the AUC for identifying HCCs from NCs increased to 0.914 with a sensitivity of 77.5% and specificity of 91.8%. High expression of BIRC5 gene is not only correlated with poor prognosis of HCCs, but also significantly associated with infiltration of immune cells, DNA methylation, and gene mutation. Conclusion: The findings suggest that the anti-BIRC5 autoantibody could serve as a potential biomarker for ANHCC, in addition to its supplementary role alongside AFP in the diagnosis of HCC. Next, we can carry out specific verification and explore the function of anti-BIRC5 autoantibody in the occurrence and development of HCC. [ABSTRACT FROM AUTHOR]

Aim: To predict the prognosis of gastric cancer patients with triple-negative tumor markers. Materials & methods: Prognostic factors of the nomogram were identified through univariate and multivariate Cox regression analyses. Calibration and receiver operating characteristic curves were used to assess accuracy. Decision curve analysis and concordance indexes were utilized to compare the nomogram with the pathological tumor, node, metastasis stage. Results: A nomogram incorporating log odds of positive lymph nodes, tumor size and lymphocyte-to-monocyte ratio was constructed. The calibration and receiver operating characteristic curves (area under the curve >0.85) showed high accuracy in predicting overall survival. The concordance indexes (0.832 vs 0.760; p < 0.001) and decision curve analysis demonstrated that the nomogram was superior to the pathological tumor, node, metastasis stage. Conclusion: A prediction and risk stratification nomogram has been developed and validated for gastric cancer patients with triple-negative tumor markers. [ABSTRACT FROM AUTHOR]

Simple Summary: Circulating tumor cells (CTCs) are cancer cells released from the primary tumor into the bloodstream, and contain cancer stem cells. The present study demonstrates the significance of a specific variant, CD44v9, in CTCs, and its combined effects with preoperative carcinoembryonic antigen (CEA) values on the prognosis of colorectal cancer (CRC). Analysis of the serum CEA levels and the expression of CD44v9 mRNA in CTCs, followed by evaluation of their association with clinicopathological factors, showed the association of CD44v9 mRNA with liver metastasis. Furthermore, patients with CD44v9-positive CTCs showed a poorer prognosis than those with CD44v9-negative CTCs. Combining CD44v9 mRNA expression with CEA values provided more detailed prognostic information. These results suggest that CD44v9 mRNA expression in CTCs, alongside CEA levels, could serve as a valuable prognostic marker for CRC, and could potentially lead to the development of more personalized treatment strategies against CRC. Circulating tumor cells (CTCs) are cancer cells released from the primary tumor into the bloodstream, and contain cancer stem cells that influence tumor survival, recurrence, and metastasis. Here, we investigated CD44v9 expression in CTCs and impact of preoperative carcinoembryonic antigen (CEA) levels on colorectal cancer (CRC) prognosis. We analyzed the expression of CD44v9 mRNA in CTCs using reverse transcription-polymerase chain reaction and preoperative CEA levels in blood samples obtained from 300 patients with CRC. Subsequently, we evaluated the association of CD44v9 expression and CEA levels with clinicopathological factors. CD44v9 mRNA was expressed in 31.3% of the patients, and was significantly associated with liver metastasis. Patients with positive CD44v9 expression had a lower 5-year survival rate (62.3%) than those with negative CD44v9 expression (82.8%, p < 0.001). Cox regression analysis identified CD44v9 expression and high CEA levels (≥5 ng/mL) as poor prognostic factors, while negative CD44v9 expression and low CEA levels (<5 ng/mL) were associated with favorable prognosis (hazard ratio = 0.285, p = 0.006). These results suggest that a combination of CD44v9 mRNA expression in CTCs and serum CEA levels could serve as a valuable prognostic marker for CRC, potentially enhancing the accuracy of prognosis predictions. [ABSTRACT FROM AUTHOR]

Background: The serum level of Krebs von den Lungen-6 (sKL-6) is a biomarker of interstitial pneumonia and has been reported to be elevated in patients with cancers. However, there have been few cases of gastric cancer (GC) with elevated sKL-6 that were treated by chemotherapy. We herein report two cases of GC with elevated sKL-6 that were treated with oxaliplatin plus S-1 (SOX) chemotherapy and discussed the resulting changes in sKL-6. Case presentation: The first patient was a 79-year-old woman complaining of loss of appetite. Esophagogastroduodenoscopy (EGD) showed a type-3 tumor in the gastric antrum and biopsy specimens showed adenocarcinoma. Computed tomography (CT) showed multiple liver metastases. sKL-6 was elevated to 1,292 U/ml, but a CT revealed no obvious lesions of the lungs, including interstitial pneumonia. The tumor was diagnosed as GC with liver metastases and elevated sKL-6. Respiratory function data were normal. SOX therapy using oxaliplatin and S-1 was performed. After 3 courses of SOX therapy, CT showed reductions of the liver metastases as well as the primary tumor, and sKL-6 was decreased to 201 U/ml. After the 44 courses, sKL-6 was slightly elevated. Chest CT showed interstitial pneumonia and chemotherapy was stopped. The patient is still alive without any metastasis 72 months later. The second patient was a 69-year-old woman complaining of upper abdominal pain. EGD revealed a type-3 tumor in the gastric antrum showing adenocarcinoma with HER2-positive pathology. CT showed multiple node metastases around the abdominal aorta. sKL-6 was elevated to 2,239 U/ml, but a respiratory function test showed no abnormalities, and CT of the lungs showed no obvious lesions. The tumor was diagnosed as GC with distant node metastases and elevated sKL-6. The patient received SOX therapy combined with trastuzumab. After 6 courses, the size of the primary tumor and multiple node metastases were reduced, and sKL-6 was decreased to 284 U/ml. Conclusions: These two cases suggest that sKL-6 may be important not only as an indicator of interstitial pneumonia in chemotherapeutic courses, but also as a tumor marker in GC patients with multiple metastases. [ABSTRACT FROM AUTHOR]

Background: To examine standardized uptake valuemax of the primary lesion (pSUVmax) and tumor markers (TMs) for clinically predicting distant metastasis in novo lung adenocarcinoma. Methods: The current retrospective observational study examined individuals diagnosed with de novo lung adenocarcinoma at Shanxi Cancer Hospital between February 2015 and December 2019. Results: Totally, 532 de novo lung adenocarcinoma cases were included. They were aged 60.8 ± 9.7 years and comprised 224 women and 268 patients with distant metastasis. The areas under the curves (AUCs) of pSUVmax, lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA), cytokeratin‐19 fragment (CYFRA21‐1), carbohydrate antigen 125 (CA125), and Grade of TMs for predicting distant metastasis were 0.742, 0.601, 0.671, 0.700, 0.736, and 0.745, respectively. The combination of pSUVmax, LDH, CEA, CYFRA21‐1, CA125, and grade of TMs in predicting distant metastasis had an AUC value of 0.816 (95%CI: 0.781–0.851), with sensitivity of 89.2%, specificity of 58.7%, positive predictive value of 73.7%, and negative predictive value of 79.7%, respectively. Conclusions: pSUVmax combined with serum levels of LDH, CEA, CYFRA21‐1, CA125, and the grade of TMs may have good performance in predicting distant metastasis of de novo lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the diagnostic efficacy of contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) combined with tumor markers alpha-fetoprotein (AFP) and des-γ-carboxyl prothrombin (DCP) for primary hepatic carcinoma (PHC). A total of 70 patients with PHC (PHC group), 42 patients with liver cyst (benign liver disease group (BLDG)) and 30 healthy people (healthy group (HG)) were selected as the research objects. CEUS and DCE-MRI were performed by American GE Vivid E9 color Doppler ultrasound system and Siemens 1.5T magnetic resonance imager, respectively. The levels of AFP and DCP were detected by ABBOTT i2000SR chemiluminescence instrument and enzyme-linked immunoassay (ELISA), respectively. In DCE-MRI examination, the portal phase and prolonged phase were mostly low signal in T1-weighted imaging (T1WI) sequence, and arterial phase was mostly high signal in T2WI sequence. In CEUS, most lesions showed hyper-enhancement in arterial phase, and hypo-enhancement in portal phase and delayed phase. AFP and DCP levels in PHC group were significantly higher than that in BLDG group and HG group. There were statistically significant differences among the three groups. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of combined diagnosis were statistically significant when compared with CEUS, AFP and DCP alone and either AFP or DCP positive. CEUS, DCE-MRI combined with tumor markers AFP and DCP have high sensitivity, specificity and accuracy in the diagnosis of PHC, which can more accurately diagnose the lesion type, provide basis for further treatment, and is worthy of clinical application. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) is the most frequently overexpressed receptor histologically exhibited by oral squamous cell carcinoma (OSCC) patients. Aberrated EGFR signaling may lead to recurrence and metastasis, thus laying the foundation of targeted therapy. Deactivating EGFR is likely to prevent downstream signaling thus resulting in apoptosis. Tyrosine kinase inhibitors (TKIs) have come into play to revert aggressiveness of OSCC. We exploited comparative proteomic analyses based on anti‐EGFR potential of varlitinib, using cellular proteomes from treated and untreated groups of oral cancer cells to identify protein players functional during oral carcinogenesis. Following separation by two-dimensional electrophoresis, differentially expressed cellular proteins (varlitinib-treated and untreated cells) were analyzed and later identified using QTOF mass spectrometer. In silico analysis for protein–protein interaction was carried out using STRING. Six differentially expressed proteins were identified as binding immunoglobulin protein (BiP), heat shock protein 7 C (HSP7C), protein disulfide isomerase 1 A (PDIA1), vimentin (VIME), keratin type I cytoskeletal 14 (K1C14), and β-Actin (ACTB). Relative expression of five proteins was found to be downregulated upon varlitinib treatment, whereas only K1C14 was upregulated in treated cells compared to control. Protein network analysis depicts the interaction between BiP, PDIA1, VIME, etc. indicating their role in oral carcinogenesis. Oral cancer cells show proteome shift based on varlitinib treatment compared to corresponding controls. Our data suggest candidature of varlitinib as a potent therapeutic agent and BiP, PDIA1, HSP7C, VIME, and β-Actin as complementary/prognostic markers of OSCC. [ABSTRACT FROM AUTHOR]

Purpose: The NY‐ESO‐1 antigen is highly immunogenic and often spontaneously induces an immune response in patients with cancer. We conducted a large‐scale multicenter cohort study to investigate the utility of serum NY‐ESO‐1 and p53 antibodies as predictive markers for the postoperative recurrence of gastric cancer. Here, we examined the usefulness of pre‐treatment NY‐ESO‐1 and p53 antibodies as tumor markers for the diagnosis of gastric cancer in combination with carcinoembryonic antigen (CEA) and carbohydrate antigen 19‐9 (CA19‐9). Methods: A total of 1031 patients with cT3‐4 gastric cancer were enrolled in the study. NY‐ESO‐1 and p53 antibodies were assessed prior to treatment. The positivity of NY‐ESO‐1 and p53 antibodies, CEA, and CA19‐9 was evaluated before treatment. Results: Serum NY‐ESO‐1 and p53 antibodies were positive in 12.6% and 18.1% of the patients, respectively. Positive NY‐ESO‐1 antibody response was correlated with male gender, higher cStage, and upper tumor location. However, a positive p53 antibody response was not associated with tumor factors. The combination of NY‐ESO‐1 or p53 antibody response with CEA and CA19‐9, or the 4‐factors, was positive in 45.1%, 49.6%, and 53.8% of patients, respectively. Moreover, the 4‐factor combination was able to detect >60% of cStage III‐IV diseases, which was 14% higher than that with the combination of CEA and CA19‐9. Conclusion: The combination of NY‐ESO‐1 and p53 antibody responses to CEA and CA19‐9 increases the diagnostic accuracy of gastric cancer. Serum NY‐ESO‐1 and p53 antibodies may be useful tumor markers for gastric cancer. [ABSTRACT FROM AUTHOR]