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Background: Carbohydrate antigen 125 (CA125) is a proteolytic fragment of MUC-16 that is increased in heart failure (HF) and associated with inflammation, fluid overload, and worse adverse events. Our main objective was to study the expression of CA125 on epicardium and its association with inflammation, adipogenesis, and fibrosis., Methods: Epicardial fat biopsies and blood were obtained from 151 non-selected patients undergoing open heart surgery. Immunohistochemistry, ELISA, or real-time PCR were used for analyzing protein or mRNA expression levels of CA125 and markers of inflammatory cells, fibroblasts, and adipocytes. Epithelial or stromal cells from epicardium were isolated and cultured to identify CA125 and its association with the adipogenesis and fibrosis pathways, respectively., Results: The median age was 71 (63-74) years, 106 patients (70%) were male, and 62 (41%) had an established diagnosis of HF before surgery. The slice of epicardial fat biopsy determined a positive and colorimetric staining on the epithelial layer after incubating with the CA125 M11 antibody, providing the first description of CA125 expression in the human epicardium. Epicardial CA125 showed a strong and positive correlation with markers of inflammation and fibrosis in the epicardial fat tissue while exhibiting a negative correlation with markers of the adipogenesis pathway. This relationship remained significant after adjusting for potential confounders such as a prior HF diagnosis and plasma CA125 levels., Conclusion: Epicardial cells express CA125, which is positively associated with inflammatory and fibroblast markers in epicardial adipose tissue. These results suggest that CA125 may be biologically involved in HF progression (transition from adipogenesis to fibrosis)., (© 2024. The Author(s).)

Background: HE4 and CA 125 are identified as a potential biomarker for the detection of some diseases with fibrosis., Objectives: The purpose of this pilot study was to evaluate the value of human epididymis protein 4 (HE4) and cancer antigen-125 (CA-125) in otosclerosis patients., Material and Methods: The study population consisted of 60 people (30 otosclerosis patients, 30 control group). We collected blood samples for HE4 and CA-125 levels. Serum HE4 and CA-125 levels were measured by enzyme-linked immunosorbent assay (ELISA). We compared the results between otosclerosis patients and the normal subject. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic value., Results: There was no differences in CA-125 level between the otosclerosis (20.3 U/mL [10.4-42.1] and control group (19.3 U/mL [15.3-49.8]) ( p  > 0.05). HE4 level was significantly higher in the otosclerosis group (60.9 pmol/L [32.1-101.8])] than the control group (25.3 pmol/L [12.4-91.9]) ( p  < 0.001). The AUC in ROC analysis of HE4 was 0.768 ( p  < 0.001)., Conclusions and Significance: Serum HE4 level may be a useful biomarker in otosclerosis. Further studies with a larger number of patients are required to confirm our pilot results.

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.)

Objectives: To investigate ultrasound features and the best cut-off value of the cancer antigen 125/carcinoembryonic antigen (CA125/CEA) ratio to discriminate ovarian metastases from benign and primary malignant ovarian neoplasms in two selected groups of morphological ovarian masses, namely multilocular masses with five or more locules and multilocular-solid masses., Methods: Patients with multilocular (five or more locules) or multilocular-solid ovarian masses, operated on within 3 months of ultrasound examination, and with tumor markers (CEA and CA125) available at diagnosis, were identified retrospectively from three ultrasound centers. The masses were described using the International Ovarian Tumor Analysis (IOTA) terminology. Ultrasound and clinical characteristics were compared between those with an ovarian neoplasm (including benign and primary malignant neoplasms) and those with an ovarian metastasis. Receiver-operating characteristics curve (ROC) analysis was used to evaluate the ability of CA125, CEA and CA125/CEA to differentiate between ovarian neoplasms and ovarian metastases, and their predictive performance was assessed., Results: In total, 350 (88.4%) patients with an ovarian neoplasm (including 99 benign, 43 borderline and 197 primary epithelial ovarian carcinomas, seven malignant rare tumors and four other types of invasive ovarian tumor) and 46 (11.6%) patients with an ovarian metastasis were analyzed. On ultrasound examination, ovarian neoplasms were smaller than ovarian metastases (median largest diameter, 97 (range, 20-387) mm vs 146 (range, 43-259) mm, respectively; P < 0.0001) and presented with a lower number of cysts with > 10 locules (18.9% vs 54.3%; P < 0.0001). ROC curve analysis showed that the best cut-off value of CEA for distinguishing between ovarian neoplasms and ovarian metastases was 2.33 ng/mL. The predictive performance of this CEA cut-off value was: area under the curve (AUC), 0.791 (95% CI, 0.711-0.870); accuracy, 73.7%; sensitivity, 73.1%; specificity, 78.3%; positive predictive value (PPV), 96.2%; and negative predictive value (NPV), 27.7%. The best cut-off value of CA125/CEA for distinguishing between ovarian neoplasms and ovarian metastases was 11.92. The predictive performance of this CA125/CEA cut-off value was: AUC, 0.758 (95% CI, 0.683-0.833); accuracy, 79.8%; sensitivity, 82.3%; specificity, 60.9%; PPV, 94.1%; and NPV, 31.1%., Conclusions: CA125/CEA ratio and CEA alone did not show any significant difference in their ability to distinguish between ovarian neoplasms (including benign and malignant) and ovarian metastases in masses with multilocular and those with multilocular-solid morphology. Therefore, in this morphological subgroup of ovarian masses, CEA alone is sufficient to differentiate between ovarian neoplasms and ovarian metastases. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

Introduction: The role of serum tumor markers in the modern management of advanced NSCLC remains poorly described., Methods: A single-center retrospective analysis of available carcinoembryonic antigen, CA125, CA19.9, and CA27.29 levels at baseline and during treatment of stage IV lung adenocarcinoma by oncogenic driver was conducted., Results: A total of 142 patients were analyzed (60 with anaplastic lymphoma kinase gene [ALK] rearrangement, 50 with EGFR mutation, four with ROS1 rearrangement, and 29 with KRAS mutation). Of these, 82% had at least one marker (95% if all four markers were measured), with CA27.29 being the most commonly increased and CA19.9 the rarest. Only CA27.29 differed significantly by oncogene (it was less common in KRAS) (p = 0.016). The median times to nadir during tyrosine kinase inhibitor (TKI) therapy in EGFR and ALK cases were 16.4 and 20 weeks, respectively. Of the 41 patients with EGFR mutation or ALK or ROS1 rearrangement, 24 (59%) demonstrated an initial increase within the first 4 weeks of TKI therapy, 58% of whom then had their levels fall below baseline. An increase in marker level of 10% or more from nadir occurred in 53% of systemic and 22% of central nervous system-only progression., Conclusions: Serum tumor markers are frequently increased in lung adenocarcinoma regardless of driver oncogene. Changes within the first 4 weeks of therapy may be misleading. Progression is associated with marker increases, especially in sites other than the central nervous system., (Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: Although endometriosis is a benign disease, it shares some features with cancers, such as invasiveness and the potential to metastasize. This study sought to investigate the epithelial-mesenchymal transition status in human endometriotic lesions., Material and Methods: Thirteen endometriosis patients and 10 control women without endometriosis undergoing surgery for benign indications were recruited. We examined the expression of E-cadherin, vimentin, and epithelial-mesenchymal transition-induced transcriptional factors, such as Snail and ZEB1, by immunohistochemistry. We evaluated the expression of each marker in epithelial cells of both endometriotic lesions (ovarian endometrioma, deep infiltrating endometriosis, adenomyosis) and normal endometria. The correlation between ZEB1 expression and serum level of CA125 was also investigated., Results: Immunohistochemical analysis revealed that although E-cadherin, vimentin, and Snail were expressed in epithelia of normal endometria and endometriotic lesions, ZEB1 expression was only expressed in epithelia of endometriotic lesions. Additionally, ZEB1 was most frequently observed in epithelial cells of invasive endometriosis. The endometriosis patients with high serum CA125 level were more likely to have ZEB1-positive lesions., Conclusions: This is the first observation of ZEB1 expression in epithelial cells of benign disease. The preferential expression of ZEB1 in epithelial cells of endometriotic lesions suggests that these cells may have, at least in part, a higher level of mesenchymal features possibly via ZEB1-driven epithelial-mesenchymal transition than normal endometria and that ZEB1 can be a potential indicator of invasiveness or severity of endometriosis., (© 2017 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: To investigate the diagnostic potentials of the serum levels of nine different biomarkers in endometriosis., Study Design: In this case-controlled, prospective clinical study, 80 women underwent laparoscopy or laparotomy with a preliminary diagnosis of chronic pelvic pain, severe secondary dysmenorrhea, infertility, pelvic endometriosis or pelvic mass. The 60 women with confirmed pelvic endometriosis constituted the endometriosis group, and the other 20 women without endometriosis constituted the control group. Preoperative blood samples were obtained for serum biomarker measurements. Serum levels of nine different serum biomarkers including α-enolase, macrophage migration inhibitory factor, leptin, interleukin-8, anti-endometrial antibody, phosphoinositide dependent protein kinase 1, CA125, syntaxin-5, and laminin-1 were measured concurrently and compared between the control and endometriosis groups, and among control group and endometriosis subgroups including stage I, stage II, stage III and stage IV endometriosis., Results: The serum levels of α-enolase, macrophage migration inhibitory factor, leptin, interleukin-8 and antiendometrial antibodies showed a statistically significant difference neither between control and endometriosis groups nor among control group and endometriosis subgroups. The serum levels of CA125, syntaxin-5 and laminin-1 showed a statistically significant difference both between the control and endometriosis groups (p<0.01) and among control group and endometriosis subgroups (p<0.01). Serum levels of laminin-1 in stage II and IV endometriosis; syntaxin-5 in stage I and II endometriosis; and CA125 in stage III and IV endometriosis were found to have the different levels compared to control group., Conclusions: These findings show that the concurrent measurement of CA125, syntaxin-5 and laminin-1 might be a useful non-invasive test in strengthening the diagnosis of endometriosis and in predicting its severity., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objectives: We have recently described a predictive/prognostic model for ovarian cancer, exploiting commonly available clinico-pathological parameters and the ovarian serum biomarkers mesothelin (MSL), human epididymis protein 4 (HE4) and cancer-antigen 125 (CA125). Considering urine as a prototype non- invasive sample, we investigated whether serum levels of these biomarkers are mirrored in urine and compared their clinical relevance in matched serum vs. urine samples. Methods: MSL, HE4 and CA125 were quantified in urinary (n=172) and matched serum samples (n=188) from ovarian cancer patients (n=192) using the Lumipulse ® G chemiluminescent enzyme immunoassay (Fujirebio). Results: While absolute concentrations of MSL or CA125 were higher in serum than in matched urine samples, HE4 concentrations were considerably higher in urine than in serum. Nonetheless, the levels of all three biomarkers strongly correlated between matched serum vs. urine samples and were unrelated to BRCA1/2 mutational status. Consequently, prediction of surgical outcome or relapse/death by MSL, HE4 or CA125 was similarly efficient among urinary- vs. serum-based detection. HE4 provided the highest capacity to predict surgical outcome or relapse/death among both body fluids (urine: AUC=0.854; serum: AUC=0.750, respectively). All clinically relevant findings regarding the investigated urinary biomarkers were equally reproducible among raw vs. creatinine-normalized datasets, suggesting that normalization may have subordinate priority for urine-based analysis of these biomarkers. Conclusion: We report that the capacity of MSL, HE4 and CA125 to predict surgical outcome and relapse/death is equivalent between serum vs. urine-based detection. Urinary biomarkers, in particular HE4, may provide an additional dimension for prognostic modeling in ovarian cancer. [ABSTRACT FROM AUTHOR]

Epidermoid cyst of the spleen is a rare disease, and relatively few cases were reported by literatures. Most published case reports provided inadequate information on the impact of splenic epidermoid cyst on tumor markers. A 32-year-old woman with a giant splenic epidermoid cyst was reported, for whom the serum concentration of a collection of tumor markers (CA19-9, CEA, CA125, CA242, and CA50) increased abruptly accompanied by left upper abdominal pain for 5 days. After comprehensive preoperative examination and multidisciplinary team discussion, we ruled out any concurrent malignancy and a laparoscopic total splenectomy was performed, during which the splenic cyst spontaneously ruptured unexpectedly. After surgery, the elevated serum tumor marker levels decreased sharply until reaching normal range 3 months later. Learning from the case, we conclude that interval monitoring of serum tumor markers is of critical value for patients with splenic epidermoid cyst. Abrupt elevation of tumor marker levels and abdominal pain may serve as signs of cyst rupture, which is strongly indicative of surgical intervention as soon as possible. Total removal of the splenic cyst is strongly suggested considering the recurrence and malignant potential of the splenic epidermoid cyst. [ABSTRACT FROM AUTHOR]

Cancer antigen 125 (CA125) is a serum marker associated with ovarian cancer. Despite its widespread use, CA125 levels can also be elevated in benign conditions. Recent reports suggest that detecting serum CA125 that carries the Tn antigen, a truncated O -glycan containing only N -acetylgalactosamine on serine or threonine residues, can improve the specificity of ovarian cancer diagnosis. In this study, we engineered cells to express CA125 with a Tn antigen. To achieve this, we knocked out C1GALT1 and SLC35A1 , genes encoding Core1 synthase and a transporter for cytidine-5′-monophospho-sialic acid respectively, in human embryonic kidney 293 (HEK293) cells. In ClGALT1-SLC35A1-knockout (KO) cells, the expression of the Tn antigen showed a significant increase, whereas the expression of the T antigen (galactose-β1,3- N -acetylgalactosamine on serine or threonine residues) was decreased. Due to the inefficient secretion of soluble CA125, we employed a glycosylphosphatidylinositol (GPI) anchoring system. This allowed for the expression of GPI-anchored CA125 on the cell surface of ClGALT1-SLC35A1-KO cells. Cells expressing high levels of GPI-anchored CA125 were then enriched through cell sorting. By knocking out the PGAP2 gene, the GPI-anchored form of CA125 was converted to a secretory form. Through the engineering of O -glycans and the use of a GPI-anchoring system, we successfully produced CA125 with Tn antigen modification. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer is the most lethal of all gynecological cancers. Cancer Antigen 125 (CA125) is the best‐performing ovarian cancer biomarker which however is still not effective as a screening test in the general population. Recent literature reports additional biomarkers with the potential to improve on CA125 for early detection when using longitudinal multimarker models. Methods: Our data comprised 180 controls and 44 cases with serum samples sourced from the multimodal arm of UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Our models were based on Bayesian change‐point detection and recurrent neural networks. Results: We obtained a significantly higher performance for CA125–HE4 model using both methodologies (AUC 0.971, sensitivity 96.7% and AUC 0.987, sensitivity 96.7%) with respect to CA125 (AUC 0.949, sensitivity 90.8% and AUC 0.953, sensitivity 92.1%) for Bayesian change‐point model (BCP) and recurrent neural networks (RNN) approaches, respectively. One year before diagnosis, the CA125–HE4 model also ranked as the best, whereas at 2 years before diagnosis no multimarker model outperformed CA125. Conclusions: Our study identified and tested different combination of biomarkers using longitudinal multivariable models that outperformed CA125 alone. We showed the potential of multivariable models and candidate biomarkers to increase the detection rate of ovarian cancer. [ABSTRACT FROM AUTHOR]

BACKGROUND: Therapeutic possibilities for non-small cell lung cancer (NSCLC) have considerably increased during recent decades. OBJECTIVE: To summarize the prognostic relevance of serum tumor markers (STM) for early and late-stage NSCLC patients treated with classical chemotherapies, novel targeted and immune therapies. METHODS: A PubMed database search was conducted for prognostic studies on carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA 21-1), neuron-specific enolase, squamous-cell carcinoma antigen, progastrin-releasing-peptide, CA125, CA 19-9 and CA 15-3 STMs in NSCLC patients published from 2008 until June 2022. RESULTS: Out of 1069 studies, 141 were identified as meeting the inclusion criteria. A considerable heterogeneity regarding design, patient number, analytical and statistical methods was observed. High pretherapeutic CYFRA 21-1 levels and insufficient decreases indicated unfavorable prognosis in many studies on NSCLC patients treated with chemo-, targeted and immunotherapies or their combinations in early and advanced stages. Similar results were seen for CEA in chemotherapy, however, high pretherapeutic levels were sometimes favorable in targeted therapies. CA125 is a promising prognostic marker in patients treated with immunotherapies. Combinations of STMs further increased the prognostic value over single markers. CONCLUSION: Protein STMs, especially CYFRA 21-1, have prognostic potential in early and advanced stage NSCLC. For future STM investigations, better adherence to comparable study designs, analytical methods, outcome measures and statistical evaluation standards is recommended. [ABSTRACT FROM AUTHOR]

Objective: To explore the association between CA125 and dysmenorrhea in adenomyosis, and the factors affecting CA125 in adenomyosis. Methods: Patients were grouped a the presence of dysmenorrhea. The receiver operating characteristic (ROC) curve was applied to assess the utility of CA125 for dysmenorrhea. Binary logistic regression was employed to identify the factors associating dysmenorrhea and CA125 level. Results: Patients in the dysmenorrhea group had higher CA125 levels than those in the non‐dysmenorrhea group. For those with dysmenorrhea, CA125 levels of diffuse subtype group were higher than those of the focal subtype group. The CA125 level of 35 U/mL was validated as the optimal cut‐point for dysmenorrhea in ROC curves. Compared with patients whose CA125 was 35 U/mL or less, those with CA125 levels greater than 35 U/mL were more likely to have dysmenorrhea. Thereafter, the multiple regression analysis showed that adenomyotic lesion volume was positively correlated with CA125 level in the total cohort and subtype groups, while age was negatively correlated with CA125 level in the total cohort and diffuse subtype. Conclusions: The pathogenesis of adenomyosis is not clear. CA125 was associated with dysmenorrhea in adenomyosis, and, furthermore, CA125 level is positively correlated with the severity of the disease. Synopsis: CA125 was associated with dysmenorrhea and, in addition, its level was positively correlated with adenomyotic lesion volume and negatively correlated with age. [ABSTRACT FROM AUTHOR]

Background: In this study, we intend to retrospectively analyze the clinical data of postoperative neuroblastoma children, including the results of follow-up examinations and laboratory tests, to explore the clinical value of combined serum Carbohydrate antigen 125 (CA125), neuron-specific enolase (NSE) and 24-hour urine vanillylmandelic acid (VMA) levels at baseline for the prediction of recurrence in children with neuroblastoma. Methods: 265 children with neuroblastoma were successfully followed up, including 163 cases without recurrence (non-recurrence group) and 102 cases with recurrence (recurrence group). The levels of 24-hour urine VMA were determined using spectrophotometric methods. Additionally, the serum levels of CA125 and NSE were measured using electrochemiluminescence immunoassay. Results: The serum CA125, NSE and 24-hour urine VMA levels were significantly higher in the recurrence group than in the non-recurrence group. It demonstrated a significant positive correlation between the levels of serum CA125, NSE, and 24-hour urine VMA in all children with neuroblastoma. All children in stage IV of neuroblastoma had the highest level of serum CA125, NSE and 24-hour urine VMA and vice versa. The combined CA125, NSE and VMA had significantly better sensitivity and specificity than an individual marker. Conclusions: Combined serum CA125, NSE and 24-hour urine VMA had the potential to predict neuroblastoma recurrence more effectively. [ABSTRACT FROM AUTHOR]

Objectives: Patients with adnexal masses suspicious for malignancy benefit from referral to oncology specialists during presurgical assessment of the mass. OVA1 is a multivariate assay using a five‐biomarker panel which offers high overall and early‐stage sensitivity. However, OVA1 has a high false‐positive rate for benign masses. Overa, a second‐generation multivariate index assay was developed to reduce the false‐positive rate. The aim of the present study was to use Overa as a reflex for OVA1 and increase specificity. Methods: OVA1 cut‐off scores were established to place patients into three categories: low, intermediate, and high cancer risk. Samples with intermediate‐risk OVA1 scores were reflexed to the Overa and defined as high or low risk. This protocol was tested with 1035 prospectively collected serum samples and validated with an independent prospectively collected sample set (N = 207). Results: Thirty‐five per cent (359) of samples had intermediate OVA1 scores. Reflexing these to Overa eliminated 58% of the false‐positives and improved the overall specificity from 50% to 72%. This finding was confirmed in the independent dataset, in which the specificity increased from 56% to 73%. Conclusions: Reflexing samples with intermediate OVA1 scores significantly decreases the false‐positive rate, thereby reducing unnecessary surgical referrals. Synopsis: Reflexing intermediate‐risk OVA1 scores to Overa reduces false‐positives without significant loss of sensitivity for ovarian cancer risk assessment. [ABSTRACT FROM AUTHOR]

Abstract Background Resistance to chemotherapy continues to be a challenge when treating epithelial ovarian cancer (EOC), contributing to low patient survival rates. While CA125, the conventional EOC biomarker, has been useful in monitoring patients’ response to therapy, there are no biomarkers used to predict treatment response prior to chemotherapy. Previous work in vitro showed that plasma gelsolin (pGSN) is highly expressed in chemoresistant EOC cell lines, where it is secreted in small extracellular vesicles (sEVs). Whether sEVs from tumour cells are secreted into the circulation of EOC patients and could be used to predict patient chemoresponsiveness is yet to be determined. This study aims to identify if sEV-pGSN in the circulation could be a predictive biomarker for chemoresistance in EOC. Methods Sandwich ELISA was used to measure pGSN concentrations from plasma samples of 96 EOC patients (primarily high grade serous EOC). sEVs were isolated using ExoQuick ULTRA and characterized using western blot, nanoparticle tracking analysis, and electron microscopy after which pGSN was measured from the sEVs. Patients were stratified as platinum sensitive or resistant groups based on first progression free interval (PFI) of 6 or 12 months. Results Total circulating pGSN was significantly decreased and sEV-pGSN increased in patients with a PFI ≤ 12 months (chemoresistant) compared to those with a PFI > 12 months (chemosensitive). The ratio of total pGSN to sEV-pGSN further differentiated these groups and was a strong predictive marker for chemoresistance (sensitivity: 73.91%, specificity: 72.46%). Predetermined CA125 was not different between chemosensitive and chemoresistant groups and was not predictive of chemoresponsiveness prior to treatment. When CA125 was combined with the ratio of total pGSN/sEV-pGSN, it was a significant predictor of chemoresponsiveness, but the test performance was not as robust as the total pGSN/sEV-pGSN alone. Conclusions Total pGSN/sEV-pGSN was the best predictor of chemoresponsiveness prior to treatment, outperforming the individual biomarkers (CA125, total pGSN, and sEV-pGSN). This multianalyte predictor of chemoresponsiveness could help to inform physicians’ treatment and follow up plan at the time of EOC diagnosis, thus improving patients’ outcomes.

The blood levels of cancer antigen 125 (CA125) and human epididymal secretory protein 4 (HE4) are measured in the diagnosis and progression monitoring of ovarian cancer (OC), and the Risk of Ovarian Malignancy Algorithm (ROMA) score% values are calculated for cancer risk assessment. For the first time, disposable dual screen-printed carbon electrodes modified with reduced graphene oxide, polythionine, and gold nanoparticles were used to fabricate label-free electrochemical dual CA125-HE4 immunosensors for the sensitive, fast, and practical simultaneous determination of CA125 and HE4. DPV and SWV methods were used to simultaneously determine antigens in two different linear ranges (1–100 pg mL−1 and 1–50 ng mL−1). High sensitivity, low LOD, and LOQ were obtained for two linear ranges with a correlation coefficient above 0.99. The application stability of the dual CA125-HE4 immunosensors was determined as 60 days, and the storage stability was determined as 16 weeks. The dual immunosensors exhibited high selectivity in eight different antigen mixtures. The reusability of the dual immunosensors has been tested up to 9 cycles. ROMA score% values for pre-menopausal and post-menopausal status were calculated using the concentration of CA125 and HE4 in the blood serum and assessing OC risk. The disposable dual immunosensors can be used in point-of-care tests for rapid and practical simultaneous determination of CA125 and HE4 with high selectivity, sensitivity, and repeatability. [ABSTRACT FROM AUTHOR]

BACKGROUND: Borderline ovarian tumors (BOTs) and early clinical stage malignant adnexal masses can make sonographic diagnosis challenging, while the clinical utility of tumor markers, e.g., CA125 and HE4, or the ROMA algorithm, remains controversial in such cases. OBJECTIVE: To compare the IOTA group Simple Rules Risk (SRR), the ADNEX model and the subjective assessment (SA) with serum CA125, HE4 and the ROMA algorithm in the preoperative discrimination between benign tumors, BOTs and stage I malignant ovarian lesions (MOLs). METHODS: A multicenter retrospective study was conducted with lesions classified prospectively using subjective assessment and tumor markers with the ROMA. The SRR assessment and ADNEX risk estimation were applied retrospectively. The sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR−) were calculated for all tests. RESULTS: In total, 108 patients (the median age: 48 yrs, 44 postmenopausal) with 62 (79.6%) benign masses, 26 (24.1%) BOTs and 20 (18.5%) stage I MOLs were included. When comparing benign masses with combined BOTs and stage I MOLs, SA correctly identified 76% of benign masses, 69% of BOTs and 80% of stage I MOLs. Significant differences were found for the presence and size of the largest solid component (p = 0.0006), the number of papillary projections (p = 0.01), papillation contour (p = 0.008) and IOTA color score (p = 0.0009). The SRR and ADNEX models were characterized by the highest sensitivity (80% and 70%, respectively), whereas the highest specificity was found for SA (94%). The corresponding likelihood ratios were as follows: LR+ = 3.59 and LR− = 0.43 for the ADNEX; LR+ = 6.40 and LR− = 0.63 for SA and LR+ = 1.85 with LR− = 0.35 for the SRR. The sensitivity and specificity of the ROMA test were 50% and 85%, respectively, with LR+ = 3.44 and LR− = 0.58. Of all the tests, the ADNEX model had the highest diagnostic accuracy of 76%. CONCLUSIONS: This study demonstrates the limited value of diagnostics based on CA125 and HE4 serum tumor markers and the ROMA algorithm as independent modalities for the detection of BOTs and early stage adnexal malignant tumors in women. SA and IOTA methods based on ultrasound examination may present superior value over tumor marker assessment. [ABSTRACT FROM AUTHOR]

Two-dimensional materials-based field-effect transistors (FETs) are promising biosensors because of their outstanding electrical properties, tunable band gap, high specific surface area, label-free detection, and potential miniaturization for portable diagnostic products. However, it is crucial for FET biosensors to have a high electrical performance and stability degradation in liquid environments for their practical application. Here, a high-performance InSe-FET biosensor is developed and demonstrated for the detection of the CA125 biomarker in clinical samples. The InSe-FET is integrated with a homemade microfluidic channel, exhibiting good electrical stability during the liquid channel process because of the passivation effect on the InSe channel. The InSe-FET biosensor is capable of the quantitative detection of the CA125 biomarker in breast cancer in the range of 0.01–1000 U/mL, with a detection time of 20 min. This work provides a universal detection tool for protein biomarker sensing. The detection results of the clinical samples demonstrate its promising application in early screenings of major diseases. [ABSTRACT FROM AUTHOR]

Highlights • Serum biomarkers can help to distinguish benign from malignant pelvic masses • We evaluated the diagnostic value of adding HE4, CA125 and ROMA to ultrasound for detecting ovarian cancer • In stage III and IV ovarian cancer all three biomarkers showed excellent performance • ROMA and HE4 performed better than CA125 in the differential diagnosis of ovarian cancer and endometriosis

Background: Resistance to chemotherapy continues to be a challenge when treating epithelial ovarian cancer (EOC), contributing to low patient survival rates. While CA125, the conventional EOC biomarker, has been useful in monitoring patients' response to therapy, there are no biomarkers used to predict treatment response prior to chemotherapy. Previous work in vitro showed that plasma gelsolin (pGSN) is highly expressed in chemoresistant EOC cell lines, where it is secreted in small extracellular vesicles (sEVs). Whether sEVs from tumour cells are secreted into the circulation of EOC patients and could be used to predict patient chemoresponsiveness is yet to be determined. This study aims to identify if sEV-pGSN in the circulation could be a predictive biomarker for chemoresistance in EOC. Methods: Sandwich ELISA was used to measure pGSN concentrations from plasma samples of 96 EOC patients (primarily high grade serous EOC). sEVs were isolated using ExoQuick ULTRA and characterized using western blot, nanoparticle tracking analysis, and electron microscopy after which pGSN was measured from the sEVs. Patients were stratified as platinum sensitive or resistant groups based on first progression free interval (PFI) of 6 or 12 months. Results: Total circulating pGSN was significantly decreased and sEV-pGSN increased in patients with a PFI ≤ 12 months (chemoresistant) compared to those with a PFI > 12 months (chemosensitive). The ratio of total pGSN to sEV-pGSN further differentiated these groups and was a strong predictive marker for chemoresistance (sensitivity: 73.91%, specificity: 72.46%). Predetermined CA125 was not different between chemosensitive and chemoresistant groups and was not predictive of chemoresponsiveness prior to treatment. When CA125 was combined with the ratio of total pGSN/sEV-pGSN, it was a significant predictor of chemoresponsiveness, but the test performance was not as robust as the total pGSN/sEV-pGSN alone. Conclusions: Total pGSN/sEV-pGSN was the best predictor of chemoresponsiveness prior to treatment, outperforming the individual biomarkers (CA125, total pGSN, and sEV-pGSN). This multianalyte predictor of chemoresponsiveness could help to inform physicians' treatment and follow up plan at the time of EOC diagnosis, thus improving patients' outcomes. [ABSTRACT FROM AUTHOR]

Introduction: The common type of cancer among women is epithelial ovarian carcinoma (EOC); this is because there aren't sufficient early diagnostic indicators. Each tumor marker has a special set of use for screening, diagnosing, evaluating response to therapy, and monitoring for cancer recurrence. Objective: The aim of the current is to assess role of biochemical markers in diagnosis of ovarian cancer patients, such as serum total sialic acid, Glycoprotein, Ferritin, and Cancer Antigen 125. Additionally, the impacts of oxidative stress in cancer cells that initiate apoptotic pathways will be investigated. Patients and Methods: The participants of this study comprised 36 women with epithelial ovarian cancer patients, and 36 women with benign ovarian mass (pathological controls). Other 36 women were considered normal healthy controls, who attended for treatment in Al-Amal National Cancer Hospital from January 2022 till June 2022. Results: Epithelial ovarian cancer patients had a mean age of 52.8 (SD 9.7) years, and benign ovarian mass (pathological controls) had a mean age of 49.6 (SD 5.9) years. Normal healthy controls had mean age of 50.7 (SD 3.8) years. Serum TSA, glycoprotein, ferritin, and CA-125, can provides useful information for patients in a diagnosis of ovarian cancer particularly in early-stage disease. Ferritin discriminates between healthy controls and patients with epithelial ovary cancer's, particularly in early-stage disease. In order to test for EOC, serum ferritin and CA125 together offer highest level of diagnostic efficiency. Conclusion: Early identification and diagnosis of metastasis in women with ovarian cancer is beneficial for therapy and can be utilized to determine why cancer cells develop chemoresistance. [ABSTRACT FROM AUTHOR]

In recent decades many potential serum biomarkers have been assessed in the diagnosis of ovarian cancer. Except cancer antigen 125 (CA125) and human epididymis protein 4 (HE4), none of them have been applied to everyday clinical practice. Based on extensive scientific evidence, CA125 combined with HE4 to form the risk of ovarian malignancy algorithm (ROMA), have become widespread in clinical practice in the evaluation of adnexal masses. Early ovarian cancer is often asymptomatic, so it remains challenging to develop even more effective methods for early diagnosis and screening. Among others, OVA1 is tested as a potential tool to improve the stratification of the risk of ovarian cancer. Also, a lot of effort is being made to develop suitable methods to monitor ovarian cancer patients. Serum CA125 already plays an established role in monitoring the treatment (except targeted therapies) and relapse setting in ovarian cancer patients, with a more limited role in subtypes other than in high-grade serous carcinoma, and always in correlation with imaging and clinical assessment. Human epididymis protein 4 (as well as circulating tumour DNA – ctDNA) is not recommended for monitoring at that timepoint, although encouraging newly published studies might influence their role in the future.

Context: Epithelial ovarian cancer (EOC) is a serious gynecological issue worldwide and its late detection is the major encumbrance in treatment procedures. Hypermethylation-mediated BRCA1 gene silencing results in failure of the repair system of damaged DNA playing an important role in ovarian carcinogenesis. BRCA1 gene hypermethylation can serve as a safe and highly specific clinical marker for EOC.Aims: The present study was conducted to evaluate the promoter hypermethylation of BRCA1 gene in EOC patients.Settings and Design: This hospital-based case-control study carried out in the tertiary care hospital in New Delhi. Subjects and Methods: Promoter hypermethylation of BRCA1 gene was examined in 30 EOC diagnosed untreated cases confirmed by histopathological examinations and compared with 30 normal healthy controls matched for age using methylation specific-polymerase chain reaction.Results: We found significantly higher BRCA1 promoter hypermethylation in the serum of EOC cases as compared to controls with P < 0.0001. BRCA1 gene methylation was found to have 70% sensitivity for the diagnosis of EOC with 100% specificity. A significant difference was observed in the range of CA125 levels, B12 and Folate levels between EOC cases and controls.Conclusions: We conclude that BRCA1 gene is significantly hypermethylated in EOC patients and thus can prove to be a noninvasive diagnostic tool. Our results provide prefatory evidence that epithelial ovarian epigenome can be influenced by dietary nutrients. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the deadliest gynecological cancer, leading to over 152,000 deaths each year. A late diagnosis is the primary factor causing a poor prognosis of ovarian cancer and often occurs due to a lack of specific symptoms and effective biomarkers for an early detection. Currently, cancer antigen 125 (CA125) is the most widely used biomarker for ovarian cancer detection, but this approach is limited by a low specificity. In recent years, multimarker panels have been developed by combining molecular biomarkers such as human epididymis secretory protein 4 (HE4), ultrasound results, or menopausal status to improve the diagnostic efficacy. The risk of ovarian malignancy algorithm (ROMA), the risk of malignancy index (RMI), and OVA1 assays have also been clinically used with improved sensitivity and specificity. Ongoing investigations into novel biomarkers such as autoantibodies, ctDNAs, miRNAs, and DNA methylation signatures continue to aim to provide earlier detection methods for ovarian cancer. This paper reviews recent advancements in molecular biomarkers for the early detection of ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: To evaluate the diagnostic value of adding human epididymis protein 4 (HE4), cancer antigen 125 (CA125) and risk of malignancy algorithm (ROMA) to ultrasound for detecting ovarian cancer in patients with a pelvic mass.Methods: This was a prospective, observational, multicenter study. Patients aged > 18 years who were scheduled to undergo surgery for a suspicious pelvic mass had CA125 and HE4 levels measured prior to surgery, in addition to a routine transvaginal ultrasound scan. The diagnostic performance of CA125, HE4 and ROMA for distinguishing between benign and malignant adnexal masses was assessed using receiver operating characteristic (ROC) analysis and the corresponding area under the curve (AUC).Results: Of 965 evaluable patients, 804 were diagnosed with benign tumors and 161 were diagnosed with ovarian cancer. In late-stage ovarian cancer, CA125, HE4 and ROMA all had an excellent diagnostic performance (AUC > 0.92), whereas in stage I and II, diagnostic performance of all three biomarkers was less adequate (AUC < 0.77). In the differential diagnosis of ovarian cancer and endometriosis, ROMA and HE4 performed better than CA125 with 99 and 98.1% versus 75.0% sensitivity, respectively, at 75.4% specificity.Conclusions: ROMA and HE4 could be valuable biomarkers to help with the diagnosis of ovarian cancer in premenopausal patients in order to differentiate from endometriosis, whereas CA125 may be more adequate for postmenopausal patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Women with suspected endometrial cancer undergo investigations that can be painful and anxiety-provoking. These tests are avoidable, as only 5–10% of symptomatic women have underlying cancer. A simple and accurate urine-based test to triage symptomatic women in the community will improve patient care. In this study, we evaluated the performance of two proteins (CA125 and HE4) for the detection of endometrial cancer in urine samples of 153 symptomatic women. We discovered that both proteins were significantly elevated in the urine of women with cancer compared to those without cancer. Urine CA125 performed better than HE4 in detecting endometrial cancer. When we combined urine CA125 and endometrial thickness measurement by transvaginal ultrasound scan, there was improvement in the detection of endometrial cancer. This is the first study to evaluate the performance of these proteins in urine for endometrial cancer detection. Confirmation in a larger sample is needed. A simple, noninvasive and accurate detection tool that can triage women with suspected endometrial cancer for definitive testing will transform patient care. The aim of this study was to evaluate urine CA125 and HE4 levels for the detection of endometrial cancer in symptomatic women. This was a cross-sectional diagnostic accuracy study of 153 symptomatic women who underwent urgent diagnostic investigations for suspected endometrial cancer at a large gynecological cancer center. Urine samples were collected prior to routine clinical procedures. Urine CA125 and HE4 levels were determined using automated chemiluminescent enzyme immunoassays. Univariate and multivariable receiver operating characteristic (ROC) curve analyses were performed. Urine CA125 and HE4 were discovered to be significantly elevated in women with endometrial cancer, compared to controls (p < 0.001 and p = 0.01, respectively). Urine CA125 and HE4 detected endometrial cancer with an area under the ROC curve (AUC) of 0.89 (0.81, 0.98) and 0.69 (0.55, 0.83), respectively. CA125 exhibited good discriminatory potential for Type I and early-stage tumors (AUC 0.93 and 0.90, respectively). A diagnostic model that combined urine CA125 and transvaginal ultrasound-measured endometrial thickness predicted endometrial cancer with an AUC of 0.96 (0.91, 1.00). Urine CA125 displays potential as a diagnostic tool for symptomatic women with suspected endometrial cancer. When combined with transvaginal ultrasound-measured endometrial thickness, this patient-friendly, urine-based test could help triage women for invasive diagnostics or safe reassurance, reducing costs and improving patient experience. [ABSTRACT FROM AUTHOR]

Adhesion is a significant biological characteristic of endometriosis, and accurate evaluation of the pelvic adhesion is necessary for surgical treatment. Serum CA125 is yet the most common used biomarker in the diagnosis and follow-up of patients with endometriosis despite of its high false-positive rate and low specificity. Herein, we aimed to examine the diagnostic value of the combination of the platelet-to-lymphocyte ratio (PLR) and CA125 for patients with different stages of endometriosis and their correlations with pelvic adhesion. We retrospectively analyzed the clinical data and blood count parameters of patients with both endometriosis and other benign ovarian tumors. The mean level of CA125, the PLR and the combined marker (the CA125 level multiplied by the PLR) in the EMs group were significantly higher than those in the Cyst group (P < 0.05). ROC curve analysis was used to compare the diagnostic values of serum PLR, CA125, and the combined marker in ovarian endometriosis. The cut-off value of the PLR was 176.835, with 28.3% sensitivity and 96.9% specificity. The cut-off value of CA125 was 31.67 U/mL, with 84.1% sensitivity and 87.4% specificity. The cut-off value of the combined marker was 3894.97, with 83.4% sensitivity and 95.8% specificity. It was found that the severity of adhesion in endometriosis was positively correlated with the PLR (r = 0.286, P < 0.01), CA125 (r = 0.276, P < 0.01), and combined marker (r = 0.369, P < 0.01). The combined marker showed the highest AUC value (0.751, 95% CI: 0.666–0.837), with a sensitivity of 56.0% and a specificity of 89.6%, and the cut-off value was 9056.94. Besides, the levels of CA125, PLR, and their combination were significantly elevated in patients with endometriosis. The combined marker was not only positively correlated with pelvic adhesion but also showed a greater diagnostic value and specificity than CA125 alone. These findings indicate that the combined marker may be a potential inflammatory biomarker playing an important role in the diagnosis and assessment of adhesion in endometriosis. [ABSTRACT FROM AUTHOR]

Background: Studies have found that c-Met plays a critical role in the progression of solid tumors. This study aimed to investigate the expression of c-Met in gastric cancer (GC) and its correlation with preoperative serum tumor markers and prognosis, in order to provide a more theoretical basis for targeting c-Met in the treatment of GC. Methods: Ninety-seven patients who underwent curative gastrectomy in our hospital from December 2013 to September 2015 were included in this study. The tissue microarray was constructed by paraffin-embedded tumor tissue of enrolled patients, including 97 GC points and 83 paracancerous points. Then, it was used for c-Met immunohistochemical staining, followed by an immunological H-score. The clinical baseline data and 5-year survival of patients with low and high c-Met expression were compared. Besides, the correlation between the expression of c-Met in tumor tissues and preoperative serum tumor markers was investigated. Finally, multivariate Cox regression analysis was used to explore the survival risk factors of patients. Results: c-Met has a high expression rate in GC tissues 64.95% (63/97). The expression of c-Met was significantly different in different clinicopathological stages (p < 0.05); the high expression group also had a higher M stage and clinicopathological stage of GC. The correlation test between the c-Met H-score and CA125 was statistically significant (p = 0.004), indicating a positive correlation. Furthermore, high c-Met expression correlated with poor overall survival (OS) for 5 years (p = 0.005). It was also found that the high expression of c-Met in stage I–II patients was correlative with poor OS for 5 years (p = 0.026), while stage III–IV patients had no statistical significance (p > 0.05). Multivariate Cox regression analysis showed that c-Met might be an independent risk factor for survival 5 years after surgery. Conclusion: This study found that the high expression of c-Met in GC tissues was associated with poor 5-year OS in GC patients and was an independent risk factor for 5-year survival after curative gastrectomy. The expression of c-Met in GC tissues was also positively correlated with preoperative serum CA125. [ABSTRACT FROM AUTHOR]

PurposeCancer antigen 125 (CA125) is a glycoprotein expressed by epithelial cells of several normal tissue types and overexpressed by several epithelial cancers. Serum CA125 levels are mostly used as an aid in the diagnosis of ovarian cancer patients, to monitor response to treatment and detect cancer recurrence. Besides tumor characteristics, CA125 levels are also influenced by several epidemiologic factors, such as age, parity, and oral contraceptive use. Identifying factors that influence CA125 levels in ovarian cancer patients could aid in the interpretation of CA125 values for individuals.MethodsWe evaluated predictors of pretreatment CA125 in 13 studies participating in the Ovarian Cancer Association Consortium. This analysis included a total of 5,091 women with invasive epithelial ovarian cancer with pretreatment CA125 measurements. We used probit scores to account for variability in CA125 between studies and linear regression to estimate the association between epidemiologic factors and tumor characteristics and pretreatment CA125 levels.ResultsIn age-adjusted models, older age, history of pregnancy, history of tubal ligation, family history of breast cancer, and family history of ovarian cancer were associated with higher CA125 levels while endometriosis was associated with lower CA125 levels. After adjusting for tumor-related characteristics (stage, histology, grade), body mass index (BMI) higher than 30 kg/m2 was associated with 10% (95% CI 2, 19%) higher CA125 levels, while race (non-white vs. white) was associated with 15% (95% CI 4, 27%) higher CA125 levels.ConclusionOur results suggest that high BMI and race may influence CA125 levels independent of tumor characteristics. Validation is needed in studies that use a single assay for CA125 measurement and have a diverse study population.

• Surface imprinted PPy-NT based chemosensor was devised for CA125 biomarker determination. • CA125 imprinted PPy nanotubes were synthesized via vapor deposition polymerization. • The chemosensor sensitivity and selectivity towards the CA125 biomarker were favorable. In this study, an electrochemical chemosensor that utilizes a conductive polymer-based molecularly imprinted polymer (MIP) surface for rapid and reliable determination of CA125 was devised. A novel method has been applied to fabricate CA125 imprinted polypyrrole nanotubes (MI-PPy NT) via vapor deposition polymerization (VDP) as a recognition element for highly selective and sensitive determination of CA125. The chemosensor was prepared by immobilizing MI-PPy NT onto screen-printed gold electrodes (Au-SPE) and the performance of the sensor was evaluated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) in terms of selectivity, sensitivity, linear dynamic concentration range (LDR) and limit of detection (LOD). The MI-PPy NT@Au-SPE sensor exhibited high sensitivity (68.57 μA per decade) to the CA125 concentration ranging from 0.1 U mL−1 to 100 U mL−1 at an LOD of 0.4 U mL−1 with a correlation coefficient of 0.9922. The developed chemosensors with their novel design combined with a facile fabrication method, prove to be promising as future state-of-the-art biosensors. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovarian cancer (OC) is the deadliest genital tumor in women. In this multicenter study, we developed three new diagnostic models based on serum proteins and patient age. All models were then validated using data from centers other than those used for the model development. We also compared the performance of these models with common singular markers (CA125, HE4) and algorithms (ROMA-50 and the Copenhagen Index). We used modern technology (Luminex®, Austin, TX, USA) that enables the simultaneous determination of several biomarkers in a small amount of blood. A combination of patient age with four to six markers performed best: CA125, osteopontin, prolactin, macrophage migration inhibitory factor, and, eventually, HE4 and leptin. Our models were better than the ROMA-50 index but did not outperform the Copenhagen Index. In postmenopausal patients, all the newly developed models performed excellently. Unfortunately, none of the models tested improved the diagnosis in premenopausal patients and those missed due to normal CA125 levels. Ovarian cancer (OC) is the most lethal genital malignancy in women. We aimed to develop and validate new proteomic-based models for non-invasive diagnosis of OC. We also compared them to the modified Risk of Ovarian Malignancy Algorithm (ROMA-50), the Copenhagen Index (CPH-I) and our earlier Proteomic Model 2017. Biomarkers were assessed using bead-based multiplex technology (Luminex®) in 356 women (250 with malignant and 106 with benign ovarian tumors) from five European centers. The training cohort included 279 women from three centers, and the validation cohort 77 women from two other centers. Of six previously studied serum proteins (CA125, HE4, osteopontin [OPN], prolactin, leptin, and macrophage migration inhibitory factor [MIF]), four contributed significantly to the Proteomic Model 2021 (CA125, OPN, prolactin, MIF), while leptin and HE4 were omitted by the algorithm. The Proteomic Model 2021 revealed a c-index of 0.98 (95% CI 0.96, 0.99) in the training cohort; however, in the validation cohort it only achieved a c-index of 0.82 (95% CI 0.72, 0.91). Adding patient age to the Proteomic Model 2021 constituted the Combined Model 2021, with a c-index of 0.99 (95% CI 0.97, 1) in the training cohort and a c-index of 0.86 (95% CI 0.78, 0.95) in the validation cohort. The Full Combined Model 2021 (all six proteins with age) yielded a c-index of 0.98 (95% CI 0.97, 0.99) in the training cohort and a c-index of 0.89 (95% CI 0.81, 0.97) in the validation cohort. The validation of our previous Proteomic Model 2017, as well as the ROMA-50 and CPH-I revealed a c-index of 0.9 (95% CI 0.82, 0.97), 0.54 (95% CI 0.38, 0.69) and 0.92 (95% CI 0.85, 0.98), respectively. In postmenopausal women, the three newly developed models all achieved a specificity of 1.00, a positive predictive value (PPV) of 1.00, and a sensitivity of >0.9. Performance in women under 50 years of age (c-index below 0.6) or with normal CA125 (c-index close to 0.5) was poor. CA125 and OPN had the best discriminating power as single markers. In summary, the CPH-I, the two combined 2021 Models, and the Proteomic Model 2017 showed satisfactory diagnostic accuracies, with no clear superiority of either model. Notably, although combining values of only four proteins with age, the Combined Model 2021 performed comparably to the Full Combined Model 2021. The models confirmed their exceptional diagnostic performance in women aged ≥50. All models outperformed the ROMA-50. [ABSTRACT FROM AUTHOR]

Endometriosis or adenomyosis can be clinically diagnosed by ultrasound, symptoms, physical examination, and serum CA125. The urinary markers need to be investigated. The aim of our study was to investigate the urinary markers of clinical endometriosis/adenomyosis, and the correlation of serum CA125 was also studied. From the literature, alpha-1 antitrypsin (A1AT), enolase-1, vitamin D binding protein (VDBP), and CA125 in urine and serum were used in our study and measured by enzyme-linked immunosorbent assays (ELISA). Further clinical correlation and detection performance were evaluated. We enrolled 19 normal controls and 33 patients clinically diagnosed with endometriosis/adenomyosis. There were significant differences between studied patients and normal controls, as follows: serum CA125 (130.91 vs. 19.75 U/mL, p = 0.004); urinary CA125-creatinine ratio (5.591 vs. 0.254 ng/mg, p = 0.028); and urinary VDBP-creatinine ratio (28.028 vs. 7.301 ng/mg, p = 0.018). For diagnostic performances, serum CA125 provided the best results, with an area under curve (AUC) of 0.888 (p = 0.001) and accuracy of 86.5%. Other excellent results were also found using urinary VDBP (AUC 0.841, p = 0.001) and A1AT (AUC 0.722, p = 0.011) creatinine ratio. Using three combined biomarkers, serum CA125, urinary VDBP, and A1AT creatinine ratio, provided good detection power (AUC 0.913, p = 0.001, sensitivity 90.9%, specificity 76.5%). Double urine markers used in combination with VDBP and A1AT creatinine ratio also provided good diagnostic performance (AUC 0.809, p = 0.001, sensitivity 81.8%, specificity 76.5%, accuracy 80%). Further development of non-invasive point-of-care tests using these biomarkers could be a fruitful future endeavor. [ABSTRACT FROM AUTHOR]

Background: Adnexal masses are a common problem seen in women. The aim of this study was to determine the appropriate cut-off for symptom-based score to predict ovarian malignancy in women with adnexal mass and to evaluate it in combination with CA125. Methods: This was a prospective study involving 341 women with adnexal mass who underwent surgery. A symptom-based scoring system was administered to the women, preoperatively, and CA125 levels were documented. Receiver operating characteristic curve (ROC) analysis was used to determine the appropriate cut-off for the symptom-based scoring. Results for this symptom-based scoring and CA125 were correlated with surgical pathological findings. Results: Out of the 341 women with adnexal mass, 112 were diagnosed to have ovarian malignancy. The mean age of women was 43.6±13.8 years. Using ROC analysis, symptom score ≥9 was determined to be the appropriate cut-off. The area under curve (AUC) at this cut-off score was found to be 0.87 (95% CI 0.83–0.91). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) at this cut-off was found to be 84.8%, 88.6%,78.5%, and 92.3%, respectively. Combining CA125 and symptom score resulted in higher sensitivity (96.4%) and NPV (97.4%) with specificity and PPV of 65.5% and 57.8%, respectively. Conclusion: Symptom score in combination with CA125 has good ability to predict ovarian malignancy in women with adnexal masses. [ABSTRACT FROM AUTHOR]

ObjectiveWe developed and validated a hybrid risk classifier combining serum markers and epidemiologic risk factors to identify post-menopausal women at elevated risk for invasive fallopian tube, primary peritoneal, and ovarian epithelial carcinoma.MethodsTo select epidemiologic risk factors for use in the classifier, Cox proportional hazards analyses were conducted using 74,786 Women's Health Initiative (WHI) Observational Study (OS) participants. To construct a combination classifier, 210 WHI OS cases and 536 matched controls with serum marker measurements were analyzed; validation employed 143 cases and 725 matched controls from the WHI Clinical Trial (CT) with similar data.ResultsAnalyses identified a combination risk classifier composed of two elevated-risk groups: 1) women with CA125 or HE4 exceeding a 98% specificity threshold; and 2) women with intact fallopian tubes, prior use of menopausal hormone therapy for at least two years, and either a first degree relative with breast or ovarian cancer or a personal history of breast cancer. In the WHI OS population, it classified 13% of women as elevated risk, identifying 30% of ovarian cancers diagnosed up to 7.8years post-enrollment (Hazard Ratio [HR]=2.6, p

In recent decades many potential serum biomarkers have been assessed in the diagnosis of ovarian cancer. Except cancer antigen 125 (CA125) and human epididymis protein 4 (HE4), none of them have been applied to everyday clinical practice. Based on extensive scientific evidence, CA125 combined with HE4 to form the risk of ovarian malignancy algorithm (ROMA), have become widespread in clinical practice in the evaluation of adnexal masses. Early ovarian cancer is often asymptomatic, so it remains challenging to develop even more effective methods for early diagnosis and screening. Among others, OVA1 is tested as a potential tool to improve the stratification of the risk of ovarian cancer. Also, a lot of effort is being made to develop suitable methods to monitor ovarian cancer patients. Serum CA125 already plays an established role in monitoring the treatment (except targeted therapies) and relapse setting in ovarian cancer patients, with a more limited role in subtypes other than in high-grade serous carcinoma, and always in correlation with imaging and clinical assessment. Human epididymis protein 4 (as well as circulating tumour DNA - ctDNA) is not recommended for monitoring at that timepoint, although encouraging newly published studies might influence their role in the future. [ABSTRACT FROM AUTHOR]

Aim: There is an urgent need to set up a useful biomarker for ovarian cancer. Galectin-1 is a promising carbohydrate-binding protein which plays a remarkable role in various malignancies yet its clinical significance is questionable. In this study, we have tested the clinical implications of serum Galectin-1 levels in patients with ovarian tumours. Main methods: Serum Galectin-1 levels were quantified in 84 newly diagnosed ovarian tumour patients and 20 healthy controls by Enzyme Linked Immuno Sorbent Assay during the course of the disease. Therefore the samples were taken at diagnosis, after surgery and after chemotherapy. Key findings: The Galectin-1 levels were found to be associated with various variables of Ovarian Cancer patients. The levels were found to be prominently high in postmenopausal patients. Galectin-1 levels were raised in epithelial ovarian tumours with significantly high levels in serous subtype. A decrease in Galectin-1 levels post-surgical intervention and after receiving chemotherapy was found. Galectin-1 levels evidently distinguished between normal, benign, malignant and metastatic cases as compared to CA125 levels. Galectin-1 demonstrated to be a better biomarker than CA125 according to the Receiver Operating Characteristic (ROC) curve analysis. Significance: The study emphasizes that serum Galectin-1 may serve as a better surrogate biomarker in Ovarian Cancer for early detection, discriminating between malignant and benign abdominal masses and monitoring the progression of the disease and response to treatment. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the trajectory of two surrogates of fluid overload –antigen carbohydrate 125 (CA125) and amino-terminal pro-brain natriuretic peptide (NT-proBNP)– after the addition of oral empagliflozin to usual care in a cohort of patients with chronic heart failure (CHF) and type 2 diabetes (T2D). From October 2015 to February 2019, 60 ambulatory patients with CHF and T2D were retrospectively included. The primary endpoint was to assess the longitudinal trajectory of plasma levels of CA125 and NT-proBNP after empagliflozin initiation. Changes in quantitative variables were evaluated using linear mixed regression. Median CA125 and NT-proBNP at baseline were 17 (11–75) U/mL and 1662 (647–4230) pg/mL, respectively. A total of 510 outpatient visits were recorded [median (interquartile range) of visits per patient: 6 (4–11)] during a median of 1.78 years. We found a significant and steady decrease in the log of CA125 after empagliflozin initiation (p < 0.001). Conversely, the log of NT-proBNP predicted trajectory did not significantly change (p = 0.425). In this cohort of patients with CHF and T2D, empagliflozin initiation was associated with a significant decrease in CA125 levels without modifying the trajectory of NT-proBNP. Considering that CA125 has emerged as a surrogate marker of tissue congestion, we hypothesize that empagliflozin might predominantly promote extravascular decongestion. • The exact mechanisms by which SGLT2i improve cardiovascular and renal outcomes remains elusive at present • One hypothesis is that these agents may differentially regulate volume content in the interstitial vs. intravascular compartment • Present findings support this hypothesis by showing an early decrease in CA125 levels after empagliflozin initiation without modifying NTproBNP [ABSTRACT FROM AUTHOR]

Congestion explains many of the signs and symptoms of acute heart failure (AHF) and disease progression. However, accurate quantification of congestion is challenging in daily practice. Antigen carbohydrate 125 (CA125) or mucin 16 (MUC16), a large glycoprotein synthesized by mesothelial cells, has emerged as a reliable proxy of congestion and inflammation in patients with heart failure (HF). In AHF syndromes, CA125 is strongly associated with right‐sided HF parameters and a higher risk of adverse clinical events beyond standard prognostic factors, including natriuretic peptides. Furthermore, CA125 has the potential for both monitoring and guide HF treatment following a decompensated HF event. The wide availability of CA125 in most clinical laboratories, together with its standardized measurement and reduced cost, makes this marker attractive for routine use in decompensated HF. Further research is required to understand better its biological role and its promising utility as a tool to guide decongestive therapy in HF. [ABSTRACT FROM AUTHOR]

Background: Tissue factor pathway inhibitor 2 (TFPI2) is a novel serum biomarker that discriminates ovarian clear cell carcinoma (CCC) from borderline ovarian tumors (BOTs) and non-clear cell epithelial ovarian cancers (EOCs). Here, we examined the performance of TFPI2 for preoperative diagnosis of CCC. Methods: Serum samples were obtained preoperatively from patients with ovarian masses, who needed surgical treatment at five hospitals in Japan. The diagnostic powers of TFPI2 and cancer antigen 125 (CA125) serum levels to discriminate CCC from BOTs, other EOCs, and benign lesions were compared. Results: A total of 351 patients including 69 CCCs were analyzed. Serum TFPI2 levels were significantly higher in CCC patients (mean ± SD, 508.2 ± 812.0 pg/mL) than in patients with benign lesions (154.7 ± 46.5), BOTs (181 ± 95.5) and other EOCs (265.4 ± 289.1). TFPI2 had a high diagnostic specificity for CCC (79.5%). In patients with benign ovarian endometriosis, no patient was positive for TFPI2, but 71.4% (15/21) were CA125 positive. TFPI2 showed good performance in discriminating stage II–IV CCC from BOTs and other EOCs (AUC 0.815 for TFPI2 versus 0.505 for CA125) or endometriosis (AUC 0.957 for TFPI2 versus 0.748 for CA125). The diagnostic sensitivity of TFPI2 to discriminate CCC from BOTs and other EOCs was improved from 43.5 to 71.0% when combined with CA125. Conclusions: High specificity of TFPI2 for preoperative detection of CCC was verified with the defined cutoff level of TFPI2 in clinical practice. TFPI2 and CA125 may contribute substantially to precise prediction of intractable CCC. [ABSTRACT FROM AUTHOR]

As an important global medical problem, hepatocellular carcinoma (HCC) has been recognized as the most frequent primary liver cancer and a leading cause of death among patients with cirrhosis. Surveillance of HCC using serum markers aims to reduce the disease-related mortality of HCC. MUC16 (mucin 16, also known as carbohydrate antigen 125, CA125) has been predicted as a tumor biomarker for many cancer types. Based on the high frequency mutation rate in a database from the Cancer Genome Atlas (TCGA), we investigated the effects of MUC16 knockdown and the regulatory profile of MUC16 in HepG2 and Huh7 cell lines. Knockdown of MUC16 was conducted via siRNA transfection, and the proliferation of cells was not affected by CCK8 assay results. Moreover, decreasing the expression of MUC16 enhanced the migration and invasion of cells, as shown by wound healing and transwell assays. Furthermore, RNA-seq was used to investigate the effect of MUC16 knockdown on the gene expression profile of HepG2 and Huh7 cells. Our study demonstrated the significant role of MUC16 in the inhibition of the migration and invasion of HepG2 and Huh7 cells. [ABSTRACT FROM AUTHOR]

Ovarian cancer is a leading cause of female mortality worldwide. Although novel approaches on this disease have been developed, overall survival rates remain moderate due to the lack of scientific evidence promoting screening at early stages of the disease. A number of biomarkers have been suggested as predictive for this type of cancer. The role of relaxin in endometrial cancer is well documented but the scientific evidence is lacking with regards to ovarian cancer. We studied patients with ovarian cancer, benign ovarian cyst and healthy patients too. The levels of relaxin have been found to be an adequate diagnostic biomarker for ovarian cancer. We also presented the different range of Ca125, HE4 and ROMA in these three groups. Randomised control trials need to be conducted though, in order to elucidate the true role of relaxin in these cases. [ABSTRACT FROM AUTHOR]

[Display omitted] • A sensitive and selective electrochemical biosensor for CA125 detection in serum was prepared; • Antifouling BSA hydrogel was prepared through the crosslinking of BSA with GA; • The biosensor based on BSAG exhibited good antifouling capability in human serum. The development of electrochemical biosensor capable of detecting specific biomarkers in real complex biological samples remains a challenge significantly relevant to a range of disease diagnostic applications. Herein an antifouling electrochemical biosensor suitable for biomarker detection in human serum was constructed based on protein hydrogels. A typical protein bovine serum albumin (BSA) was crosslinked with glutaraldehyde to form a hydrogel, which was freeze-dried and re-swollen to exhibit excellent antifouling capability. The rheological testing revealed that the prepared BSA hydrogel possessed good elasticity with a critical strain value of about 600 %, which is important for the construction of stable hydrogel-based biosensors. Following the immobilization of CA125 antibodies onto the BSA hydrogel modified electrode, an electrochemical biosensor for the detection of CA125 was constructed, with a linear range of 0.1 ∼ 1000 U mL−1 and a limit of detection of 0.026 U mL−1. Owing to the unique properties of the BSA hydrogel, the biosensor exhibited good stability and excellent antifouling performances, and it was able to detect CA125 in human serum with acceptable accuracy. The strategy of constructing low fouling biosensors based on hydrogels prepared from BSA with biocompatibility and widespread availability represented a very promising advance along the road to develop biosensing devices with robust operation in complex biological fluids. [ABSTRACT FROM AUTHOR]

Aim: The objective was to evaluate the diagnostic value of salivary biomarkers in breast cancer. Materials and methods: A prospective study was carried out of 91 consecutive breast cancer patients and 60 controls without neoplastic disease. Demographic data were recorded, along with the Hospital Anxiety Depression (HAD), risk for development periodontal diseases questionnaire and Mini-Nutritional Assessment (MNA) scores, and the TNM classification and stage of the primary tumor. Unstimulated basal saliva samples were collected and stored at − 80 °C until analysis. Results: The mean salivary CA125 concentration was 102.1 pg/ml in the control group and 267.6 pg/ml in the breast cancer group (p = 0.005). The soluble Fas (sFas) concentration in turn was 84.1 pg/ml and 145.9 pg/ml, respectively (p = 0.008). None of the biomarkers was related to questionnaire-assessed risk for development of periodontal diseases. The area under the ROC curve was 0.68 for CA125 (95% CI, 0.05–0.56) and 0.67 for sFas (95% CI, 0.08–0.55). Conclusions: The salivary biomarkers CA125 and sFas appear to be promising tools in the diagnosis of breast cancer. [ABSTRACT FROM AUTHOR]

What is known and objective: To compare short‐term therapeutic efficacies and related changes of serum markers from two chemotherapeutic regimes using lobaplatin or carboplatin in combination with paclitaxel in ovarian cancer patients after cytoreductive surgery. Methods: 120 patients were recruited with pathologically confirmed ovarian cancer. Patients were equally and randomly divided into two groups receiving paclitaxel (PTX) with lobaplatin (LBP) or carboplatin (CBP, as control), respectively, 21 days as a cycle for 6 cycles. Follow‐up was performed for 6 months post‐treatment. The therapeutic efficacy, serum levels of CA125 (cancer antigen 125/ mucin 16) and HE4 (Human epididymis protein 4) as well as the quality of life were assessment before and after treatment. Results: No significant difference in therapeutic efficacy was observed between the groups (P >.05). The response rates at 1, 3 and 6 months were 76.7%, 66.7% and 46.7% in the LBP group and 73.3%, 63.3% and 36.7% in the CPB group, respectively. At the end of chemotherapy, serum levels of HE4 and CA125 in both groups returned to normal. However, patients in the LBP group had significantly lower HE4 and CA125 levels than those in the CPB group when examined at 3 or 6 months after chemotherapy (P <.05). Moreover, at the end of follow‐up, the quality‐of‐life score (QLQ‐C30) of the LBP group was better than that of the CBP group with statistical significance (P <.05). What is new and conclusion: Both lobaplatin and carboplatin have decent anti‐tumour efficacy to be involved in the standard platinum/paclitaxel‐based chemotherapy against ovarian cancer. Lobaplatin, on the other hand, has demonstrated higher efficacy to control the progress of the disease yet less toxicity to warrant better patient quality of life. [ABSTRACT FROM AUTHOR]

Pancreatic adenocarcinoma remains one of the most lethal cancers. The only recommended biomarker CA19-9 proves to be not accurate enough to establish a certain diagnosis. Therefore, a determination of usefulness of other biomarkers is essential. Our aim was to compare the specificity and sensitivity of Ca125 and CA19-9 by means of meta-analysis. The systematic review of combined tests (CA19-9 + Ca125) was also performed.We conducted a systematic search of Medline (via PubMed) and Ovid. After screening of abstracts and the assessment of full-texts, nine studies (number of patients, n = 1599) were included. Hierarchical summary receiver under operator curve (hsROC) model was applied to estimate the diagnostic accuracy.CA19-9 sensitivity and specificity were 0.748 (95%CI 0.676–0.809) and 0.782 (95%CI 0.716–0.836), respectively. These values were estimated on 0.593 (95%CI 0.489–0.69) and 0.754 (95%CI 0.817–0.668) for Ca125. Regarding the heterogeneity of studies, a strong threshold effect for Ca125 and moderate one for CA19-9 were found.Our meta-analysis did not prove the superiority of Ca125. It should be nevertheless noted that the sparsity of studies precludes accurate analysis of various factors’ influence. The review of proposed combined tests shows that CA19-9 + Ca125 models are generally characterized by higher sensitivity. [ABSTRACT FROM AUTHOR]