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Objective: The aim of this study was to explore the clinical application value of two-dimensional ultrasound (2D-US) combined with contrast-enhanced ultrasonography (CEUS) in the differential diagnosis of benign, borderline ovarian tumors (BOTs), and malignant ovarian epithelial tumors (OETs). Methods: The clinical data of 108 patients who underwent surgery for pathologically confirmed of OETs at Peking University People's Hospital between December 2018 and November 2023 were retrospectively studied. The diagnostic value of 2D-US combined with CEUS for diagnosing OETs was analyzed using chi-square tests, receiver operating characteristic (ROC) curves, and random forest models. Results: Among the 108 cases of OETs, 23 were benign, 34 were BOTs, and 51 were malignant. Chi-square tests confirmed that the perfusion pattern of the contrast agent plays an important role in the differential diagnosis of OETs. Compared with those in the benign group, the BOTs were not significantly different in terms of perfusion phase and enhancement intensity, but the regression time of the BOTs was earlier (P < 0.05). Compared with the BOTs, the malignant tumors group showed earlier perfusion and higher enhancement intensity, with no significant difference in regression time. The ROC curve results indicated that the combined diagnostic efficiency of 2D-US and CEUS in distinguishing OETs was significantly higher than that of a single diagnostic technique in terms of sensitivity, specificity, accuracy, and AUC. The random forest model results revealed that among the various parameters used in the differential diagnosis of OETs, the perfusion pattern was the most significant factor. Conclusion: 2D-US combined with CEUS helps improve the differential diagnostic efficiency for benign, BOTs, and malignant OETs. [ABSTRACT FROM AUTHOR]

Background: Primary peritoneal carcinoma (PPC) is a rare malignancy. Clinically, its histological morphology resembles that of epithelial ovarian tumors (EOC), often leading to misdiagnosis. Diagnosis and treatment of PPC are time-sensitive because of the rapidly progressive nature of the disease. Case report: Herein, we report the case of a 54-year-old woman who was initially diagnosed with ovarian cancer; however, extensive workup showed evidence of Müllerian PPC origin. Furthermore, the patient harbored a targetable BRCA mutation. Conclusion: The patient was treated with the BRCA-targeting agents and had a good prognosis after surgery. [ABSTRACT FROM AUTHOR]

Purpose: To develop a combined diagnostic model integrating the subclassification of the 2022 version of the American College of Radiology (ACR) Ovarian-Adnexal Reporting and Data System (O-RADS) with carbohydrate antigen 125 (CA125) and to validate whether the combined model can offer superior diagnostic efficacy than O-RADS alone in assessing adnexal malignancy risk. Methods: A retrospective analysis was performed on 593 patients with adnexal masses (AMs), and the pathological and clinical data were included. According to the large differences in malignancy risk indices for different image features in ORADS category 4, the lesions were categorized into groups A and B. A new diagnostic criterion was developed. Lesions identified as category 1, 2, 3, or 4A with a CA125 level below 35 U/ml were classified as benign. Lesions identified as category 4A with a CA125 level more than or equal to 35 U/ml and lesions with a category of 4B and 5 were classified as malignant. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the curve (AUC) of O-RADS (v2022), CA125, and the combined model in the diagnosis of AMs were calculated and compared. Results: The sensitivity, specificity, PPV, NPV, accuracy, and AUCs of the combined model were 92.4%, 96.5%, 80.2%, 98.8%, 94.1%, and 0.945, respectively. The specificity, PPV, accuracy, and AUC of the combined model were significantly higher than those of O-RADS alone (all P < 0.01). In addition, both models had acceptable sensitivity and NPV, but there were no significant differences among them (P > 0.05). Conclusion: The combined model integrating O-RADS subclassification with CA125 could improve the specificity and PPV in diagnosing malignant AMs. It could be a valuable tool in the clinical application of risk stratification of AMs. [ABSTRACT FROM AUTHOR]

Background: Preoperative prediction of lymphovascular space invasion (LVSI) is crucial for improving the prognosis of patients with cervical cancer. Purpose: To evaluate the value of preoperative amide proton transfer (APT) imaging combined with serum CA125 levels for predicting LVSI in cervical cancer. Material and Methods: This retrospective study included 80 patients with cervical cancer who underwent preoperative magnetic resonance imaging, including APT imaging. Serum CA125 levels were measured using a fully automated immunoassay analyzer and chemiluminescence method. The presence of LVSI was determined based on the pathological results after surgery. Results: Among the 40 patients who met the requirements, 29 had postoperative pathological confirmation of LVSI, while 11 did not. The areas under the receiver operating characteristic curves (AUC) of preoperative APT and CA125 levels predicting LVSI were 0.889 and 0.687, respectively. When the APT value was 2.9%, the corresponding Youden index was the highest (0.702), with a sensitivity of 79.3% and specificity of 90.9%. When the critical value of the preoperative serum CA15 level was 25.3 u/mL, the corresponding Youden index was the highest (0.508), with a sensitivity of 69.0% and a specificity of 81.8%. The sensitivity and specificity of preoperative APT imaging combined with serum CA125 in predicting LVSI were 82.7% and 100%, respectively, with a Youden's index of 0.828 and an AUC of 0.923. Conclusion: The combination of preoperative APT imaging and serum CA125 levels is valuable for predicting LVSI in cervical cancer. Diagnostic efficacy is highest when the APT value is >2.9% and the serum CA125 level is >25.3 u/mL. [ABSTRACT FROM AUTHOR]

Objective: To investigate the dynamic changes of serum carbohydrate antigen 125 (CA125) and human epididymal protein 4 (HE4) levels before and after surgery and during chemotherapy, and their relationship with progression-free survival (PFS) and platinum sensitivity in patients with ovarian cancer. Methods: A retrospective analysis was conducted on serum CA125 and HE4 levels before surgery, before chemotherapy, and at least twice during chemotherapy in standardized treated patients with ovarian cancer in the gynecologic oncology department of the First People's Hospital Affiliated with Shanghai Jiao Tong University School of Medicine. Data on platinum drug sensitivity and PFS were collected. The main statistical methods included chi-square test, t-test, logistic regression analysis, and Cox proportional hazards regression analysis. Results: The analysis of 117 patients with high-grade serous ovarian cancer suggested that CA125 and HE4 positivity were associated with higher stage, greater ascites volume, unsatisfactory surgical debulking, and positive ascites cytology. Cox regression analysis verified that both CA125 and HE4 are prognostic risk factors (OR=4.29, P=0.010; OR=1.77, P=0.049). Patients with both CA125 and HE4 positive and those with only CA125 positive showed no significant difference in prognosis (P > 0.05). The half-life of CA125 and HE4 were calculated using the formula t1/2=t1 [/2×lg (c1/c2)]. The optimal cut-offs for preoperative and postoperative CA125 and HE4, and the half-life of CA125 and HE4 were determined by X-tile and were 436 U/L, 400 pmol/L, 12 U/L, 35 pmol/L, 21 days, and 25 days, respectively. The prognostic analysis showed that except for the lowest value of HE4, all other factors were related to prognosis. The highest HR value was 3.28 for CA125 half-life >21 days, with a decrease of 57.5% in median PFS (P < 0.001). The area under the curve (AUC) was calculated by plotting the receiver operating characteristic (ROC) curve. ROC curve analysis showed that CA125 half-life >21 days (AUC=0.76), CA125 lowest value >12 U/L (AUC=0.70), and failure of CA125 to return to normal after the third cycle of chemotherapy (AUC=0.71) have certain clinical value for predicting recurrence within three years, with sensitivities of 71.8%, 68.3%, and 68.2%, and specificities of 79.6%, 71.7%, and 72.6%, respectively. Conclusion: CA125 half-life, the lowest value of CA125 during chemotherapy, CA125 not returning to normal after the third cycle of chemotherapy, and having ≥ 2 positive indicators among the 6 indicators have certain clinical value in predicting recurrence within 3 years. Further exploration is needed to assess their value in predicting platinum sensitivity. [ABSTRACT FROM AUTHOR]

Pseudo-Meigs syndrome is a rare syndrome characterized by hydrothorax and ascites associated with pelvic masses, and patients occasionally present with elevated serum cancer antigen-125 (CA125) levels. Hydropic leiomyoma (HLM) is an uncommon subtype of uterine leiomyoma characterized by hydropic degeneration and secondary cystic changes. Rapidly enlarging HLMs accompanied by hydrothorax, ascites, and elevated CA125 levels may be misdiagnosed as malignant tumors. Here, we report a case of HLM in a 45-year-old Chinese woman who presented with ascites and hydrothorax. Preoperative abdominopelvic CT revealed a giant solid mass in the fundus uteri measuring 20 × 15 × 12 cm. Her serum CA125 level was elevated to 247.7 U/ml, while her hydrothorax CA125 level was 304.60 U/ml. The patient was initially diagnosed with uterine malignancy and underwent total abdominal hysterectomy and adhesiolysis. Pathological examination confirmed the presence of a uterine hydropic leiomyoma with cystic changes. After tumor removal, the ascites and hydrothorax subsided quickly, with no evidence of recurrence. The patient's serum CA125 level decreased to 116.90 U/mL on Day 7 and 5.6 U/mL on Day 40 postsurgery. Follow-up data were obtained at 6 months, 1 year, and 2 years after surgery, and no recurrence of ascites or hydrothorax was observed. This case highlights the importance of accurate diagnosis and appropriate management of HLM to achieve successful outcomes. [ABSTRACT FROM AUTHOR]

Human epididymis protein 4 (HE4) is a secretory protein encoded by the WFDC2 gene. The potential use of HE4 as a tumor marker has been supported by an increasing number of studies demonstrating an upregulation of HE4 in a range of malignant neoplasm. The aim of the study was to examine the association between the serum levels of HE4 and the clinico-pathological variables and to assess the potential use of circulatory HE4 for the diagnosis of breast cancer. An observational case-control study was carried out in P.G. Department of General Surgery, MLN Medical College, Prayagraj. Forty patients with breast cancer were taken as cases, and thirty healthy individuals were taken as controls. HE4 and CA125 were measured using ELISA test. There was a statistically significant strong positive correlation between CA125 and serum HE4 (rho = 0.7, p < 0.001) with sensitivity for predicting case of 93.33% and a specificity of 80.00% with AUROC of 0.8483. Serum HE4 does not change with progression of stages of malignancy. Serum HE4 had good diagnostic performance, and it can be used as a diagnostic marker of breast malignancy. [ABSTRACT FROM AUTHOR]

Background Heart failure with preserved ejection fraction (HFpEF) often coexists with chronic kidney disease (CKD). Exercise intolerance is a major determinant of quality of life and morbidity in both scenarios. We aimed to evaluate the associations between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and carbohydrate antigen 125 (CA125) with maximal aerobic capacity (peak VO2) in ambulatory HFpEF and whether these associations were influenced by kidney function. Methods This single-centre study prospectively enrolled 133 patients with HFpEF who performed maximal cardiopulmonary exercise testing. Patients were stratified across estimated glomerular filtration rate (eGFR) categories (<60 ml/min/1.73 m2 versus ≥60 ml/min/1.73 m2). Results The mean age of the sample was 73.2 ± 10.5 years and 56.4% were female. The median of peak VO2 was 11.0 ml/kg/min (interquartile range 9.0–13.0). A total of 67 (50.4%) patients had an eGFR <60 ml/min/1.73 m2. Those patients had higher levels of NT-proBNP and lower peak VO2, without differences in CA125. In the whole sample, NT-proBNP and CA125 were inversely correlated with peak VO2 (r  = −0.43, P  < .001 and r  = −0.22, P  = .010, respectively). After multivariate analysis, we found a differential association between NT-proBNP and peak VO2 across eGFR strata (P for interaction = .045). In patients with an eGFR ≥60 ml/min/1.73 m2, higher NT-proBNP identified patients with poorer maximal functional capacity. In individuals with eGFR <60 ml/min/1.73 m2, NT-proBNP was not significantly associated with peak VO2 [β = 0.02 (95% confidence interval −0.19–0.23), P  = .834]. Higher CA125 was linear and significantly associated with worse functional capacity without evidence of heterogeneity across eGFR strata (P for interaction = .620). Conclusions In patients with stable HFpEF, NT-proBNP was not associated with maximal functional capacity when CKD was present. CA125 emerged as a useful biomarker for estimating effort intolerance in HFpEF irrespective of the presence of CKD. [ABSTRACT FROM AUTHOR]

Noninvasive and effective methods for early screening of non‐small cell lung cancer (NSCLC) still need to be developed. At present, a reasonable conclusion is that a combination of tumor markers is a superior predictor of screening. Cytokines, as important regulators of cancer development, have great potential for the screening and prognosis of NSCLC. This study screened novel biomarkers related to the early screening and prognosis of NSCLC. In the present study, the biological significance and immunoregulation of interleukin‐24 (IL‐24) were analyzed based on The Cancer Genome Atlas data. Next, 150 serum samples from initially treated patients with NSCLC and 70 controls were collected, and we obtained pathological sections from 60 patients with NSCLC. The ELISA and immunohistochemistry results showed the differential expression of IL‐24 and carbohydrate antigen 125 (CA125). The results show that IL‐24 is an important tumor suppressor in NSCLC that helps to improve the poor prognosis of these patients. A significantly negative correlation between IL‐24 and CA125 levels was also found. Notably, serum IL‐24 levels were significantly negatively correlated with the TNM stage of patients with NSCLC, consistent with an important role for tumor suppressors in NSCLC. The receiver operating characteristic curve analysis showed that a combination of IL‐24 and CA125 was an effective panel for discriminating patients with NSCLC from HD, and individuals with other lung diseases. Serum IL‐24 and CA125 levels were identified as independent prognostic markers for NSCLC. The IL‐24 and CA125 panel exhibited good performance in the screening of NSCLC. [ABSTRACT FROM AUTHOR]

Abstract Objective The aim of this study was to explore the clinical application value of two-dimensional ultrasound (2D-US) combined with contrast-enhanced ultrasonography (CEUS) in the differential diagnosis of benign, borderline ovarian tumors (BOTs), and malignant ovarian epithelial tumors (OETs). Methods The clinical data of 108 patients who underwent surgery for pathologically confirmed of OETs at Peking University People’s Hospital between December 2018 and November 2023 were retrospectively studied. The diagnostic value of 2D-US combined with CEUS for diagnosing OETs was analyzed using chi-square tests, receiver operating characteristic (ROC) curves, and random forest models. Results Among the 108 cases of OETs, 23 were benign, 34 were BOTs, and 51 were malignant. Chi-square tests confirmed that the perfusion pattern of the contrast agent plays an important role in the differential diagnosis of OETs. Compared with those in the benign group, the BOTs were not significantly different in terms of perfusion phase and enhancement intensity, but the regression time of the BOTs was earlier (P

Abstract Pseudo-Meigs syndrome is a rare syndrome characterized by hydrothorax and ascites associated with pelvic masses, and patients occasionally present with elevated serum cancer antigen-125 (CA125) levels. Hydropic leiomyoma (HLM) is an uncommon subtype of uterine leiomyoma characterized by hydropic degeneration and secondary cystic changes. Rapidly enlarging HLMs accompanied by hydrothorax, ascites, and elevated CA125 levels may be misdiagnosed as malignant tumors. Here, we report a case of HLM in a 45-year-old Chinese woman who presented with ascites and hydrothorax. Preoperative abdominopelvic CT revealed a giant solid mass in the fundus uteri measuring 20 × 15 × 12 cm. Her serum CA125 level was elevated to 247.7 U/ml, while her hydrothorax CA125 level was 304.60 U/ml. The patient was initially diagnosed with uterine malignancy and underwent total abdominal hysterectomy and adhesiolysis. Pathological examination confirmed the presence of a uterine hydropic leiomyoma with cystic changes. After tumor removal, the ascites and hydrothorax subsided quickly, with no evidence of recurrence. The patient’s serum CA125 level decreased to 116.90 U/mL on Day 7 and 5.6 U/mL on Day 40 postsurgery. Follow-up data were obtained at 6 months, 1 year, and 2 years after surgery, and no recurrence of ascites or hydrothorax was observed. This case highlights the importance of accurate diagnosis and appropriate management of HLM to achieve successful outcomes.

Background: Inflammation has an important role in the progression of endometrial carcinoma. Aims: The aim of this study is to find the association between neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and CA125 in endometrial hyperplasia and endometrial carcinoma. The study also focuses on the association of CA125, NLR, and PLR with histopathological parameters in endometrial carcinoma that are of prognostic importance. Materials and Methods: This is a prospective cross-sectional study on 57 biopsy-proven cases of endometrial hyperplasia and carcinoma conducted over a period of two years. The NLR, PLR, and CA125 were calculated and recorded in all the 57 cases. Results: The 57 cases were divided into three groups: endometrial hyperplasia without atypia group which included 36 cases, endometrial atypical hyperplasia group which included 10 cases, and the endometrial carcinoma group which included 11 cases. Comparison was done between the groups, and parity, NLR, PLR, and CA125 were found to be significant, but patient age and postmenopausal status were not significant. NLR, PLR, and CA125 were found to increase with higher grade, pT-stage, and nodal stage for the endometrial carcinoma cases. Conclusion: NLR, PLR, and CA125 were marginally increased or normal in the case of endometrial hyperplasia without atypia and endometrial atypical hyperplasia, while they were significantly increased in endometrial carcinoma, and also correlated with an increase in grade, pT-stage, and nodal stage. Hence, these can be considered for additional screening as diagnostic, prognostic, and predictive markers in case of abnormal uterine bleeding with endometrial pathology.

Objective: To assess the treatment efficacy of dienogest specifically in the Taiwanese population with endometriosis. Materials and Methods: Eighty-eight patients diagnosed with endometriosis receiving at least 3 months of dienogest 2 mg once daily, from January 2018 to June 2022, were enrolled. They were divided into two groups: surgery group and non-surgery group. The assessment of pain improvement was based on visual analog scale (VAS) scores (0–100 mm) recorded at 0, 3, 6, and 12 months following the initiation of dienogest. Serum CA-125 value and ovarian endometrioma size were analyzed at 0 and 6 months. Results: A total of 65 patients with endometriosis presented painful symptoms. In the surgery group (N = 28), the initial VAS score was 47.5 mm, which significantly declined to 9.6 mm at 3 months (p

Abstract Global challenges in ovarian cancer underscore the need for cost-effective screening. This study aims to assess the role of pretreatment Neutrophil-to-Lymphocyte Ratio (NLR), Lymphocyte-to-Monocyte-Ratio (LMR), Platelet-to-Lymphocyte Ratio (PLR), and CA-125 in distinguishing benign and malignant ovarian tumors, while also constructing nomogram models for distinguish benign and malignant ovarian tumor using inflammatory biomarkers and CA-125. This is a retrospective study of 206 ovarian tumor patients. We conducted bivariate analysis to compare mean values of CA-125, LMR, NLR, and PLR with histopathology results. Multiple regression logistic analysis was then employed to establish predictive models for malignancy. NLR, PLR, and CA-125 exhibited statistically higher levels in malignant ovarian tumors compared to benign ones (5.56 ± 4.8 vs. 2.9 ± 2.58, 278.12 ± 165.2 vs. 180.64 ± 89.95, 537.2 ± 1621.47 vs. 110.08 ± 393.05, respectively), while lower LMR was associated with malignant tumors compared to benign (3.2 ± 1.6 vs. 4.24 ± 1.78, p = 0.0001). Multiple logistic regression analysis revealed that both PLR and CA125 emerged as independent risk factors for malignancy in ovarian tumors (P(z) 0.03 and 0.01, respectively). Utilizing the outcomes of multiple regression logistic analysis, a nomogram was constructed to enhance malignancy prediction in ovarian tumors. In conclusion, our study emphasizes the significance of NLR, PLR, CA-125, and LMR in diagnosing ovarian tumors. PLR and CA-125 emerged as independent risk factors for distinguishing between benign and malignant tumors. The nomogram model offers a practical way to enhance diagnostic precision.

Abstract 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). Graphical Abstract

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]

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). Highlights: This is the first time that CA125 was identified on human epicardium biopsies and primary culture of epithelial cells was performed. This is a promising tool for understanding the pathophysiological mechanisms association between CA-125 and HF progression. [ABSTRACT FROM AUTHOR]

Background and aim: Patients suffering from cancer are reported to have an increased risk of ischemic stroke (IS). We aimed to identify cancer-associated biomarkers found to differentiate between IS associated with cancer from those not associated with cancer. Summary of review: We performed a systematic search of PubMed and EMBASE databases according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The study is reported in PROSPERO (#CRD42022355129). In total, 5563 papers were screened, of which 49 papers were included. Seven biomarkers were identified which had the potential to differentiate between patients who had cancer or stroke or both conditions. D-dimer was the most frequently monitored biomarker, and high levels were significantly associated with cancer-related strokes in (42/44) studies. Fibrinogen was significantly associated with cancer-related strokes in 11/27 studies. A higher level of C-reactive protein, investigated in 19 studies, was associated with cancer-related strokes, but conclusive multivariate analysis was not performed. Finally, the four cancer-associated antigens CA125, CA153, CA199, and carcinoembryonic antigen were only reported on in three to six studies, respectively. These studies all originated from the Guangxi province in China. CA125 was associated with an increased risk of IS in four of six studies. Conclusion: Increased D-dimer seems associated with cancer-related IS. CRP may also be a candidate as a cancer-associated stroke biomarker, but this requires further verification. Fibrinogen and the more specific cancer biomarkers have not yet been proven helpful for detecting cancer-related strokes. [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]

Complex pelvic masses with elevated CA125 could be due to malignant and benign condition. Tubo-ovarian abscess, with irritation of the peritoneum, could increase the level of CA125 and mimic advanced ovarian cancer. Preoperatively, high accuracy radiological evaluation can reduce the high risk and unnecessary laparotomies. The patient was a 50-year-old near menopause woman with abdominal pain, fever and recent vaginal bleeding with highly elevated CA125(>4000 u/ml) and complex pelvic mass, suspected of ovarian cancer with final pathology of tubo- ovarian abscess (TOA). Misdiagnosed TOA with ovarian cancer only based on highly elevated CA_125 and performing upfront radical surgery in stable patients could result in visceral injury. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) has an unfavorable prognosis. Due to the lack of effective screening tests, new diagnostic methods are being sought to detect OC earlier. The aim of this study was to evaluate the concentration and diagnostic utility of selected matrix metalloproteinases (MMPs) as OC markers in comparison with HE4, CA125 and the ROMA algorithm. The study group consisted of 120 patients with OC; the comparison group consisted of 70 patients with benign lesions and 50 healthy women. MMPs were determined via the ELISA method, HE4 and CA125 by CMIA. Patients with OC had elevated levels of MMP-3 and MMP-11, similar to HE4, CA125 and ROMA values. The highest SE, SP, NPV and PPV values were found for MMP-26, CA125 and ROMA in OC patients. Performing combined analyses of ROMA with selected MMPs increased the values of diagnostic parameters. The topmost diagnostic power of the test was obtained for MMP-26, CA125, HE4 and ROMA and performing combined analyses of MMPs and ROMA enhanced the diagnostic power of the test. The obtained results indicate that the tested MMPs do not show potential as stand-alone OC biomarkers, but can be considered as additional tests to raise the diagnostic utility of the ROMA algorithm. [ABSTRACT FROM AUTHOR]

To investigate the diagnostic value of tuberculosis infection T cell spot test (T-SPOT.TB) combine with serum carbohydrate antigen 125 (CA125) and gamma interferon-inducible protein 10 (IP-10) in pulmonary tuberculosis with diabetes. 480 patients with suspected tuberculosis admitted to Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine from January 2021 to January 2023 were selected and divided into 166 cases in Group A (patients with tuberculosis combined with diabetes mellitus), 214 cases in Group B (patients with simple tuberculosis), and 100 cases in Group C (patients with non-tuberculous mycobacterial infection and non-diabetes mellitus) according to the diagnosis results. All subjects underwent T-SPOT. TB, and serum CA125 and IP-10 levels were detected by enzyme-linked immunosorbent assay. The diagnostic value of T-SPOT.TB combined with serum CA125 and IP-10 levels for pulmonary tuberculosis with diabetes was analyzed by drawing receiver operating characteristic (ROC) curve. The positive rate of T-SPOT.TB in group A was lower than that in group B but higher than that in group C, and the positive rate of T-SPOT. TB in group B was higher than that in group C (P＜0.05). The original values of group A antigen culture filtrate protein 10 (CFP10) and antigen 6kD early secretory antigenic target (ESAT-6) were higher than those in group B and C, and the original values of group B antigen CFP10 and antigen ESAT-6 were higher than those in group C (P＜0.05). Serum CA125 and IP-10 levels were higher in group A than in groups B and C, the serum CA125 and IP-10 levels in group B were higher than those in group C (P＜0.05). ROC curve analysis showed that, the area under the curve (AUC) of T-SPOT.TB, CA125, IP-10, T-SPOT. TB+CA125, T-SPOT.TB+IP-10 and three-term combination in the diagnosis of pulmonary tuberculosis with diabetes mellitus were 0.771, 0.769, 0.779, 0.880, 0.885 and 0.937 respectively; the AUC of three-term combination diagnosis of pulmonary tuberculosis with diabetes mellitus was greater than that of T-SPOT.TB, CA125, IP-10 alone and combination diagnosis. The positive rate of T-SPOT.TB and the levels of serum CA125 and IP-10 increased in patients with pulmonary tuberculosis with diabetes mellitus, T-SPOT. TB combined with serum CA125 and IP-10 could improve the diagnostic value of pulmonary tuberculosis with diabetes mellitus. [ABSTRACT FROM AUTHOR]

• The Risk of Ovarian Malignancy Algorithm (ROMA) has good predictive ability in distinguishing between borderline ovarian tumours (BOTs) and benign ovarian masses (BOMs) • The conventional markers, including CA125, HE4, CA724 and ROMA score, exhibit efficacy in distinguishing between high-grade serous ovarian cancer (HGSOC) and BOTs/BOMs. • Incorporating age into the ROMA score or HE4 significantly improved the predictive value for distinguishing between HGSOC and BOTs/BOMs. To develop a new algorithm for the detection of high-grade serous ovarian cancer (HGSOC). Patients diagnosed with HGSOC, borderline ovarian tumours (BOTs) or benign ovarian masses (BOMs) were enrolled between February 2019 and December 2020. Patients with BOTs or BOMs were grouped as non-HGSOC. The cases were divided randomly into a training cohort (two-thirds of cases) and a validation cohort (one-third of cases). Logistic regression was used to find risk factors for HGSOC and to create a new algorithm in the training cohort. Receiver operating characteristic curves were used to compare the diagnostic value of tumour biomarkers. Sensitivity and specificity of tumour markers and the new algorithm were calculated in the training cohort and validation cohort. This study found significant differences in age; BRCA1/2 mutation status; CA125, CA724 and HE4 levels; and Risk of Ovarian Malignancy Algorithm score between the two groups. Logistic regression analysis showed that CA125 and BRCA1/2 were risk factors for HGSOC. A new algorithm combining CA125 and BRCA1/2 increased the specificity of CA125 for diagnosis of HGSOC. The new algorithm had sensitivity of 81.08% and specificity of 93.10% in the training cohort. The new algorithm using CA125 and BRCA1/2 helped to distinguish between patients with HGSOC and patients with non-HGSOC. [ABSTRACT FROM AUTHOR]

This study aimed to analyze the diagnostic performance of serum CA-125 in acute appendicitis (AA). This review was registered in PROSPERO (CRD42023450988). We included prospective and retrospective original clinical studies evaluating the diagnostic performance of serum CA-125 in AA. A search was conducted in PubMed, Web of Science, Scopus, and OVID. Search terms and keywords were: (appendicitis OR appendectomy) AND (CA-125 OR CA125). Two independent reviewers selected the articles and extracted relevant data. Methodological quality was assessed using the QUADAS-2 index. A synthesis of the results, standardization of the metrics, and three random-effect meta-analyses were performed. Five studies with data from 533 participants (including 219 patients with a confirmed diagnosis of AA and 107 controls) were included in this review. The random-effect meta-analysis of serum CA-125 (AA vs controls) included 3 articles (125 AA and 70 controls) and resulted in a non-significant mean difference [95% CI] of – 6.80 [– 20.51, 6.92] U/mL (p = 0.33). The meta-analysis by subgroups that included only male patients resulted in a significant mean difference [95% CI] of 3.48 [0.46, 6.49] U/mL (p = 0.02). Although serum CA-125 does not appear to be a good overall marker for the diagnosis of AA, our subgroup analyses show that this marker could be useful for diagnosing AA in males. It also appears to be a potentially useful tool for discriminating complicated and uncomplicated AA. However, the limited number of included studies precludes drawing generalizable conclusions. Future prospective studies focused on males and in its potential ability to discriminate between complicated and uncomplicated AA are required. Registration. PROSPERO (CRD42023450988). [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical value of combined detection of carcinoembryonic antigen(CEA) and CA125 in the diagnosis of non-small cell lung cancer(NSCLC) combined with malignant pleural effusion. Methods: This was retrospective research. Fifty-six NSCLC patients combined with malignant pleural effusion in Baoding No.1 Hospital, China, from January 2020 to January 2022 were recruited as the malignant group, and another 56 NSCLC patients combined with pleural effusion in the same period were recruited as the benign group. Pleural effusion and serum specimens were collected from both groups and their carcinoembryonic antigen (CEA), carbohydrate antigen 125(CA125) and SP70 antigen levels were measured respectively. The differences in index levels between the two groups were compared, and the value of the index in diagnosing NSCLC combined with malignant pleural effusion was analyzed. Results: The positive rates of CEA, CA125 and SP70 antigen in pleural effusion were higher in the malignant group than in the benign group (p>0.05); The positive rates of CEA and CA125 in the malignant group were higher than those in the benign group (p>0.05), with no statistically significant difference between the two groups in the positive rates of SP70 antigen (p>0.05). ROC curve analysis revealed the value of serum CEA and CA12 in the diagnosis of NSCLC combined with malignant pleural effusion, while serum SP70 antigen had no diagnostic value (p>0.05). Conclusion: The combined detection of CEA, CA125 and SP70 antigen boasts a higher diagnostic value for NSCLC-mediated pleural effusion, with higher diagnostic value than the combined detection of serum indexes. [ABSTRACT FROM AUTHOR]

Key Clinical Message: While adenomyosis is commonly associated with a mild risk of thrombotic complications, the presence of additional thrombophilia factors can increase this risk, particularly in individuals with severe symptoms and elevated CA125 levels. [ABSTRACT FROM AUTHOR]

Liqin Yuan, Lin Cui, Jie Wang, Li Gong Department of Gynecology, Rizhao People’s Hospital, Rizhao, Shandong Province, 276800, People’s Republic of ChinaCorrespondence: Li Gong, Rizhao People’s Hospital, Rizhao, Shandong Province, 276800, People’s Republic of China, Tel +86-18663351821, Email gongli0768@163.comPurpose: Meigs’ syndrome is a rare gynecological disease characterized by the triad of benign ovarian tumor, ascites, and pleural effusion. Ovarian malignancies should be highly suspected in a postmenopausal woman with a pelvic mass, ascites, hydrothorax, and an elevated carbohydrate antigen 125 (CA125) level. It can be challenging to make a preoperative diagnosis of Meigs’ syndrome. In this report, we present a case of Meigs’ syndrome caused by an ovarian fibrothecoma and review the relevant literature to raise awareness and avoid misdiagnosis.Case Presentation: An 82-year-old woman with a 2-week history of abdominal distension was admitted to the Department of Gynecology. Ultrasound and thoracoabdominal computed tomography scans showed a left-sided hypoechoic mass in the pelvic cavity with bilateral pleural effusion and massive ascites. The CA125 concentration was 1040 U/mL (normal, 0– 35 U/mL). With a working diagnosis of ovarian malignancy, the patient underwent ultrasound-guided fine-needle puncture of the pelvic mass and paracentesis to drain the ascites. The fine-needle puncture and paracentesis fluid analysis results revealed that the ascites did not contain any tumor cells, and the pelvic mass was identified as a spindle cell tumor. Immunohistochemistry confirmed that it was a sex-cord stromal tumor. Total abdominal hysterectomy and bilateral adnexectomy were performed under general anesthesia. The pathology results confirmed the mass to have been an ovarian fibrothecoma. At the 2-month postoperative follow-up, the ascites and hydrothorax had resolved and not recurred, and the CA125 level was normal.Conclusion: Despite the high suspicion of ovarian carcinoma in postmenopausal women presenting with pelvic mass, ascites, pleural effusion, and elevated CA125, Meigs’ syndrome should be considered.Keywords: Meigs’ syndrome, ascites, pleural effusion, CA125, ovarian fibrothecoma, ovarian cancer

This study aimed to investigate the changes of serum carbohydrate antigen 125 (CA125) and prostaglandin E2 (PGE2) in patients with adenomyosis before and after treatment with high-intensity focused ultrasound (HIFU) combined with gonadotropin-releasing hormone agonist (GnRH-a). One hundred and sixty-five patients with adenomyosis who received HIFU combined with GnRH-a were selected as case group. Sixty-five healthy women who underwent physical examination at the same time were taken as normal control group. At the end of follow-up 6 months after treatment, the case group were divided into effective subgroup and ineffective subgroup according to clinical efficacy. Changes of serum CA125 and PGE2 were analyzed. Serum CA125 and PGE2 levels in the case group were higher than those in the normal control group before treatment (both P < 0.001). Serum CA125 and PGE2 levels in the case group 6 months after treatment were lower than those before treatment (both P < 0.001). There was no difference in serum CA125 and PGE2 levels between effective subgroup and ineffective subgroup before treatment (P = 0.351, 0.284, respectively). Serum CA125 and PGE2 levels in the effective subgroup were lower than those in the ineffective subgroup 6 months after treatment (both P < 0.001). Serum CA125 and PGE2 may be involved in the development of adenomyosis, and their expression levels may be related to the prognosis of patients. Levels of serum CA125 and PGE2 in patients with adenomyosis decrease after treatment with HIFU combined with GnRH-a. The detection of serum CA125 and PGE2 may be used as an index to diagnose adenomyosis and evaluate the therapeutic effect of HIFU combined with GnRH-a.

Abstract Background In patient assessment for recurrence of neoplasia, a biomarker that shows an elevated serum value before the first treatment is a candidate for follow-up examination. The biomarker squamous cell carcinoma antigen is usually utilized for follow-up of squamous cell cancer of the cervix. Case presentation We herein report a 30-year-old Japanese woman of postoperative metastasis of cervical squamous cell cancer to the mediastinal and supraclavicular lymph nodes as indicated by an elevated serum cancer antigen 125 concentration and not by the squamous cell carcinoma antigen value. After chemoradiotherapy and chemotherapy, the serum cancer antigen 125 concentration decreased to a normal value. Squamous cell carcinoma antigen was found to be distributed in both the squamous cell cancer tissue of the cervix and the supraclavicular lymph node metastatic tissue. By contrast, cancer antigen 125 was distributed in the supraclavicular lymph node metastatic tissue but not in the original squamous cell cancer tissue of the cervix. Conclusion In this case, metastasis of cervical cancer to the mediastinal and supraclavicular lymph nodes was shown by the biomarker cancer antigen 125, which was not present in the original neoplasia.

Abstract Background Mucin 16 (MUC16) overexpression is linked with cancer progression, metastasis, and therapy resistance in high grade serous ovarian cancer and other malignancies. The cleavage of MUC16 forms independent bimodular fragments, the shed tandem repeat sequence which circulates as a protein bearing the ovarian cancer biomarker (CA125) and a proximal membrane-bound component which is critical in MUC16 oncogenic behavior. A humanized, high affinity antibody targeting the proximal ectodomain represents a potential therapeutic agent against MUC16 with lower antigenic potential and restricted human tissue expression. Results Here, we demonstrate the potential therapeutic versatility of the humanized antibody as a monoclonal antibody, antibody drug conjugate, and chimeric antigen receptor. We report the crystal structures of 4H11-scFv, derived from an antibody specifically targeting the MUC16 C-terminal region, alone and in complex with a 26-amino acid MUC16 segment resolved at 2.36 Å and 2.47 Å resolution, respectively. The scFv forms a robust interaction with an epitope consisting of two consecutive β-turns and a β-hairpin stabilized by 2 hydrogen bonds. The VH-VL interface within the 4H11-scFv is stabilized through an intricate network of 11 hydrogen bonds and a cation-π interaction. Conclusions Together, our studies offer insight into antibody-MUC16 ectodomain interaction and advance our ability to design agents with potentially improved therapeutic properties over anti-CA125 moiety antibodies.

Introduction: Small cell neuroendocrine carcinoma of the prostate (SCNECP) is a rare and highly malignant tumor that commonly transforms into conventional prostate adenocarcinoma (CPAC). Most of SCNECP cases cannot be detected and diagnosed early, and SCNECP is often diagnosed when there is liver and lung metastasis. Therefore, the early detection of the process from CPAC to SCNECP is crucial. Case Report: We present a case of a 73-year-old man who was initially admitted to our hospital with metastatic CPAC. He was administered goserelin acetate 3.6 mg combined with bicalutamide tablets (50 mg) once daily for endocrine therapy and docetaxel (100 mg) combined with prednisone (5 mg) twice a day. After treatment, the prostate-specific antigen (PSA) level decreased significantly, but the CEA, CA199, and CA125 levels began to increase progressively after a short decline. However, no solid tumor recurrence was observed in multiple reexaminations. It was not until 9 months after the elevation of tumor markers that multiple metastatic lesions appeared in the liver, which finally confirmed the diagnosis of metastatic SCNECP. After chemotherapy with etoposide 360 mg combined with carboplatin 200 mg, the tumor size was significantly reduced, and tumor markers decreased. However, the remission time was only 3 months. The patient’s liver metastases continued to grow, and CEA, CA199, and CA125 levels continued to increase. Conclusion: During CPAC treatment, PSA levels continued to decrease, whereas CEA, CA199, and CA125 levels continued to increase. This suggests the possibility of the transformation of CPAC into SCNECP.

We report a case of well-differentiated papillary mesothelial tumor (WDPMT) diagnosed using internal thoracoscopic biopsy in a patient who has suffered from recurrent pleural effusions for over 35 years together with a history of elevated CA125. We hope to provide a case for the diagnosis of this rare benign and preinvasive pleural tumor and recommend that internal thoracoscopy may be a good choice in these recurrent pleural effusion patients especially for those minimal lesions not easily detected using CT scan. [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]

Objective: To investigate the evaluation value of tuberculosis infection T cell spot test (T-SPOT.TB) combined with serum adenosine deaminase (ADA), amyloid A (SAA) and carbohydrate antigen 125 (CA125) in the diagnosis and treatment outcome of active pulmonary tuberculosis (APTB). Methods: 137 APTB patients (APTB group) and 80 non-APTB patients (control group) who were admitted to Hunan Chest Hospital from October 2021 to October 2022 were selected, all APTB patients received routine anti-tuberculosis treatment, patients were divided into outcome group (92 cases) and non-outcome group (45 cases) according to the treatment outcome. T-SPOT.TB was performed, and serum ADA, SAA and CA125 levels were detected before treatment. The efficacy of T-SPOT.TB combined with serum ADA, SAA and CA125 in the diagnosis of APTB and predicting treatment outcome were analyzed by receiver operating characteristic (ROC) curve. Results: The positive rate of T-SPOT.TB and the levels of serum ADA, SAA and CA125 in APTB group were higher than those in control group(P<0.05). The positive rate of T-SPOT.TB and the levels of serum ADA, SAA and CA125 in non-outcome group were higher than those in outcome group(P<0.05). The area under the curve (AUC) of T-SPOT.TB combined with serum ADA, SAA and CA125 in diagnosing APTB and predicting its treatment outcome were 0.917 and 0.833 respectively, which were higher than those of single index. Conclusion: The positive rate of T-SPOT.TB in APTB patients increased, and the levels of serum ADA, SAA and CA125 increased, which were relate to the poor prognosis after anti-tuberculosis treatment, T-SPOT.TB combined with serum ADA, SAA and CA125 had high value in the diagnosis and treatment outcome evaluation of APTB. [ABSTRACT FROM AUTHOR]

Background: It is art important clinical means to identify benign and malignant breast diseases caused by nipple discharge through the detection and analysis of components in nipple discharge. This study was aimed to test the expression and clinical significance of carbohydrate antigen 125 (CA125), carbohydrate antigen 153 (CA153) and carcinoembryonic antigen (CEA) in nipple discharge of breast cancer patients. Methods: From January 2017 to December 2018, 86 patients with invasive ductal carcinoma of the breast with nipple discharge (breast cancer group) and 50 patients with ordinary breast duct hyperplasia with nipple discharge (benign control group) were selected, and the levels of CA125, CA153 and CEA in nipple discharge and serum were detected by electrochemiluminescence immunoassay. Results: The levels of CA125, CA153 and CEA in nipple discharge and serum in benign control group were significantly lower than those in the breast cancer group, and the levels of CA125, CA153 and CEA in serum were obviously lower than those in nipple discharge. The expression levels of CA125, CA153 and CEA in nipple discharge in the breast cancer group had no significant difference in different age of onset and different tumor sites. The CA125, CA153 and CEA levels in nipple discharge of patients with tumor diameter 5 cm, low differentiation, high stage, metastasis, and recurrence were obviously elevated versus to those of patients with tumor diameter <5 cm, high differentiation, low stage, and no metastasis and recurrence. These levels were not significantly correlated with the expression of estrogen receptor (ER) and progesterone receptor (PR), but was significantly correlated with the expression of human epidermal growth factor receptor (HER-2) and Ki-67. The accuracy, sensitivity, and negative predictive value of the combined detection of CA125, CA153 and CEA in nipple discharge in the diagnosis of breast cancer were markedly improved compared with the combined detection of serum and single detection. Conclusion: The combination of CA125, CA153 and CEA in nipple discharge can be considered as a potential diagnostic method for breast cancer, which is an effective supplement to serological diagnosis, and can provide new ideas for the differential diagnosis of benign and malignant breast cancer with nipple discharge. [ABSTRACT FROM AUTHOR]

Objective To explore the clinical significance and diagnostic value of inflammatory factors, coagulation and carbohydrate antigen 125 (CA125) in moderate to severe ovarian endometriosis cyst. Methods A retrospective analysis was conducted on clinical data from 127 patients with stage Ⅲ and Ⅳ ovarian endometriotic cysts (endometriosis group) and 101 patients with other benign ovarian cysts treated at Shenzhen Second People′s Hospital from January to December, 2021. The differences in inflammatory factors, coagulation function, and CA125 between the two groups were compared. Receiver operating characteristic (ROC) curves were drawn, and the diagnostic value of relevant indicators for moderate to severe ovarian endometriosis was analyzed. Results In the endometriosis group, the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were significantly higher than those in the control group (P＜0.05). Plasma fibrinogen (FIB) was significantly higher in the endometriosis group (P＜0.05). Thrombin time (TT) was significantly shorter in the endometriosis group (P＜0.05). CA125 and human epididymis protein 4 (HE4) were significantly higher in the endometriosis group (P＜0.05). There were no significant differences between the two groups in lymphocyte-to-monocyte ratio (LMR), platelet count (PLT), prothrombin time (PT), and activated partial thromboplastin time (APTT) (P＞0.05). Combined detection of CA125 and NLR can increase the sensitivity of diagnosis to 89.0%. Conclusion Patients with moderate to severe ovarian endometriosis exhibit changes in inflammatory factors and elevated fibrinogen. Combined detection of CA125 and NLR has clinical value in the diagnosis of moderate to severe ovarian endometriosis. [ABSTRACT FROM AUTHOR]

Background: In patient assessment for recurrence of neoplasia, a biomarker that shows an elevated serum value before the first treatment is a candidate for follow-up examination. The biomarker squamous cell carcinoma antigen is usually utilized for follow-up of squamous cell cancer of the cervix. Case presentation: We herein report a 30-year-old Japanese woman of postoperative metastasis of cervical squamous cell cancer to the mediastinal and supraclavicular lymph nodes as indicated by an elevated serum cancer antigen 125 concentration and not by the squamous cell carcinoma antigen value. After chemoradiotherapy and chemotherapy, the serum cancer antigen 125 concentration decreased to a normal value. Squamous cell carcinoma antigen was found to be distributed in both the squamous cell cancer tissue of the cervix and the supraclavicular lymph node metastatic tissue. By contrast, cancer antigen 125 was distributed in the supraclavicular lymph node metastatic tissue but not in the original squamous cell cancer tissue of the cervix. Conclusion: In this case, metastasis of cervical cancer to the mediastinal and supraclavicular lymph nodes was shown by the biomarker cancer antigen 125, which was not present in the original neoplasia. [ABSTRACT FROM AUTHOR]

Background: Mucin 16 (MUC16) overexpression is linked with cancer progression, metastasis, and therapy resistance in high grade serous ovarian cancer and other malignancies. The cleavage of MUC16 forms independent bimodular fragments, the shed tandem repeat sequence which circulates as a protein bearing the ovarian cancer biomarker (CA125) and a proximal membrane-bound component which is critical in MUC16 oncogenic behavior. A humanized, high affinity antibody targeting the proximal ectodomain represents a potential therapeutic agent against MUC16 with lower antigenic potential and restricted human tissue expression. Results: Here, we demonstrate the potential therapeutic versatility of the humanized antibody as a monoclonal antibody, antibody drug conjugate, and chimeric antigen receptor. We report the crystal structures of 4H11-scFv, derived from an antibody specifically targeting the MUC16 C-terminal region, alone and in complex with a 26-amino acid MUC16 segment resolved at 2.36 Å and 2.47 Å resolution, respectively. The scFv forms a robust interaction with an epitope consisting of two consecutive β-turns and a β-hairpin stabilized by 2 hydrogen bonds. The VH-VL interface within the 4H11-scFv is stabilized through an intricate network of 11 hydrogen bonds and a cation-π interaction. Conclusions: Together, our studies offer insight into antibody-MUC16 ectodomain interaction and advance our ability to design agents with potentially improved therapeutic properties over anti-CA125 moiety antibodies. [ABSTRACT FROM AUTHOR]

ObjectivesWe 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.MethodsMSL, 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).ResultsWhile 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.ConclusionWe 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.

Key Clinical Message While adenomyosis is commonly associated with a mild risk of thrombotic complications, the presence of additional thrombophilia factors can increase this risk, particularly in individuals with severe symptoms and elevated CA125 levels.

Background: It is an important clinical means to identify benign and malignant breast diseases caused by nipple discharge through the detection and analysis of components in nipple discharge. This study was aimed to test the expression and clinical significance of carbohydrate antigen 125 (CA125), carbohydrate antigen 153 (CA153) and carcinoembryonic antigen (CEA) in nipple discharge of breast cancer patients. Methods: From January 2017 to December 2018, 86 patients with invasive ductal carcinoma of the breast with nipple discharge (breast cancer group) and 50 patients with ordinary breast duct hyperplasia with nipple discharge (benign control group) were selected, and the levels of CA125, CA153 and CEA in nipple discharge and serum were detected by electrochemiluminescence immunoassay. Results: The levels of CA125, CA153 and CEA in nipple discharge and serum in benign control group were significantly lower than those in the breast cancer group, and the levels of CA125, CA153 and CEA in serum were obviously lower than those in nipple discharge. The expression levels of CA125, CA153 and CEA in nipple discharge in the breast cancer group had no significant difference in different age of onset and different tumor sites. The CA125, CA153 and CEA levels in nipple discharge of patients with tumor diameter 5 cm, low differentiation, high stage, metastasis, and recurrence were obviously elevated versus to those of patients with tumor diameter

Abstract Background MUC16 is a heavily glycosylated cell surface mucin cleaved in the tumor microenvironment to shed CA125. CA125 is a serum biomarker expressed by > 95% of non-mucinous advanced stage epithelial ovarian cancers. MUC16/CA125 contributes to the evasion of anti-tumor immunity, peritoneal spread and promotes carcinogenesis; consequently, it has been targeted with antibody-based passive and active immunotherapy. However, vaccination against this self-antigen likely requires breaking B cell tolerance and may trigger autoimmune disease. Display of self-antigens on virus-like particles (VLPs), including those produced with human papillomavirus (HPV) L1, can efficiently break B cell tolerance. Results A 20 aa juxta-membrane peptide of the murine MUC16 (mMUC16) or human MUC16 (hMUC16) ectodomain was displayed either via genetic insertion into an immunodominant loop of HPV16 L1-VLPs between residues 136/137, or by chemical coupling using malemide to cysteine sulfhydryl groups on their surface. Female mice were vaccinated intramuscularly three times with either DNA expressing L1-MUC16 fusions via electroporation, or with alum-formulated VLP chemically-coupled to MUC16 peptides. Both regimens were well tolerated, and elicited MUC16-specific serum IgG, although titers were higher in mice vaccinated with MUC16-coupled VLP on alum as compared to L1-MUC16 DNA vaccination. Antibody responses to mMUC16-targeted vaccination cross-reacted with hMUC16 peptide, and vice versa; both were reactive with the surface of CA125+ OVCAR3 cells, but not SKOV3 that lack detectable CA125 expression. Interestingly, vaccination of mice with mMUC16 peptide mixed with VLP and alum elicited mMUC16-specific IgG, implying VLPs provide robust T help and that coupling may not be required to break tolerance to this epitope. Conclusion Vaccination with VLP displaying the 20 aa juxta-membrane MUC16 ectodomain, which includes the membrane proximal cleavage site, is likely to be well tolerated and induce IgG targeting ovarian cancer cells, even after CA125 is shed.

Fanchun Yang, Qingying Wang, Rui Ma, Fangzhen Deng, Jie Liu Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Jie Liu, Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, No. 301, Yanchang Zhong Road, Shanghai, People’s Republic of China, Email Liujie1997@tongji.edu.cnObjective: Adenomyosis patients are in a hypercoagulable state, and studies have shown that carbohydrate antigen125 (CA125) may relate to the hypercoagulability and thrombosis of patients with adenomyosis, but there is still a lack of clarity regarding the changes in CA125-related coagulation indicators. This study was to explore the changes and influencing factors of CA125-related coagulation parameters in patients with adenomyosis.Methods: Retrospective observational study conducted on 200 patients with adenomyosis (AM group), 240 patients with uterine leiomyoma (LM group) and 81 patients with cervical intraepithelial neoplasia (CIN)-III (control group), of which the coagulation parameters were detected by clinical blood sample collection and statistical method analysis and informed consent was obtained.Results: The level of CA125 in the AM group was significantly higher than that in the LM group and control group. However, thrombin time (TT) shortened in the AM group when compared with the LM and control group. Activated partial thromboplastin time (APTT) in the AM group was shorter than in the control group. Multivariate logistic regression analysis found that adenomyosis was associated with CA125 level (OR=323.860, 95% CI 90.424– 1159.924, P< 0.001), APTT (OR=1.295, 95% CI 1.050– 1.598, P=0.016), TT (OR=0.642, 95% CI 0.439– 0.938, P=0.022), menorrhagia (OR=7.363, 95% CI 2.544– 21.315, P< 0.001), dysmenorrhea (OR=22.590, 95% CI 8.185– 62.347, P< 0.001). Correlation analysis revealed that APTT (r= − 0.207) and TT (r = − 0.174) were negatively correlated with the level of CA125.Conclusion: The shortening of CA125-related APTT and TT indicates that it is meaningful to detect coagulation parameters of patients with elevated CA125 levels early, dysmenorrhea and menorrhagia, and maybe further discover the hypercoagulability and prevent the occurrence of thrombus in adenomyosis.Keywords: adenomyosis, coagulation parameters, hypercoagulability, CA125, APTT, TT

In the Part I, we have discussed the background of CA125 and the development of anti-CA125 monoclonal antibody (MAb) to highlight the potential role of CA125 and anti-CA125 MAb in the management of women with advanced stage epithelial ovarian cancer (EOC). Glycosylation change either by N-link or by O-link of CA125 is supposed to play a role in the modification of immunity. Anti-CA125 MAb, which can be classified as OC 125-like Abs, M11-like Abs, and OV197-like Abs, is often used for diagnosing, screening, monitoring and detecting the mesothelin-related diseases of the abdominal cavity, particular for those women with EOC. Additionally, anti-CA125 MAb also plays a therapeutic role, named as OvaRex MAb-B43.13 (oregovomab), which has also been extensively reviewed in the Part I review article. The main mechanisms include (a) forming CA125 immune complexes to activate the antigen-presenting cells; (b) triggering induction of CA125-specific immune responses, including anti-CA125 Abs against various epitopes and CA125-specific B and T cell responses; and (c) triggering CD4 and CD8 T-cell responses specific for B43.13 to produce specific and non-specific immune response. With success in vitro, in vivo and in primitive studies, phase II study was conducted to test the effectiveness of chemoimmunotherapy (CIT) for the management of EOC patients. In the 97 EOC patients after optimal debulking surgery (residual tumor

A 72‐year‐old woman developed left hemiparesis, and her initial magnetic resonance imaging (MRI) showed multiple acute ischemic lesions. Although she was treated with antithrombotic therapies, follow‐up MRI showed a recurrent small ischemic stroke. Her serum CA125 level was markedly elevated, and abdominal computed tomography (CT) and MRI showed a pelvic mass lesion with pleural effusions and ascites, suggesting malignant ovarian tumor associated with Trousseau's syndrome. However, the surgical resection specimens were pathologically diagnosed as benign ovarian fibroma and serous cystadenoma, and she was finally diagnosed as having Meigs syndrome. This case suggested that Meigs syndrome with elevated CA125 levels might play a role in the development of recurrent ischemic strokes. [ABSTRACT FROM AUTHOR]

The current standard therapy of epithelial ovarian cancer (EOC) is the combination of surgery (primary cytoreductive surgery or interval cytoreductive surgery) and platinum-based chemotherapy (mainly using paclitaxel and carboplatin either by neoadjuvant chemotherapy and/or by postoperative adjuvant chemotherapy) with/without adding targeted therapy (mainly using anti-angiogenesis agent- bevacizumab). After front-line chemotherapy, the advanced-stage EOC can be successfully controlled and three-quarters of patients can achieve a complete clinical remission. Unfortunately, nearly all patients will recur and progression-free survival (PFS) of these patients is seldom more than 3 years with a dismal median PFS of 12–18 months. With each recurrence, patients finally develop resistance to standard chemotherapy regimen, contributing to fewer than half of women who survive for more than 5 years after diagnosis with a median overall survival (OS) of 40.7 months. Due to the lower PFS and OS, particularly for those advanced-stage patients, novel therapeutic options during the front-line therapy are desperately needed to decrease the occurrence of recurrence, and the majority of them are still under investigation. It is well-known that overexpression of CA125 has been associated with attenuated cellular apoptosis, platinum chemotherapy resistance, tumor proliferation and disease progression, suggesting that anti-CA125 may play a role in the management of patients with EOC. The current review is a Part I which will focus on development of anti-CA125 monoclonal antibody, hoping that alternation of the front-line therapy by chemo-immunotherapy will be beneficial for prolonged survival of patients with EOC.

Background: MUC16 is a heavily glycosylated cell surface mucin cleaved in the tumor microenvironment to shed CA125. CA125 is a serum biomarker expressed by > 95% of non-mucinous advanced stage epithelial ovarian cancers. MUC16/CA125 contributes to the evasion of anti-tumor immunity, peritoneal spread and promotes carcinogenesis; consequently, it has been targeted with antibody-based passive and active immunotherapy. However, vaccination against this self-antigen likely requires breaking B cell tolerance and may trigger autoimmune disease. Display of self-antigens on virus-like particles (VLPs), including those produced with human papillomavirus (HPV) L1, can efficiently break B cell tolerance. Results: A 20 aa juxta-membrane peptide of the murine MUC16 (mMUC16) or human MUC16 (hMUC16) ectodomain was displayed either via genetic insertion into an immunodominant loop of HPV16 L1-VLPs between residues 136/137, or by chemical coupling using malemide to cysteine sulfhydryl groups on their surface. Female mice were vaccinated intramuscularly three times with either DNA expressing L1-MUC16 fusions via electroporation, or with alum-formulated VLP chemically-coupled to MUC16 peptides. Both regimens were well tolerated, and elicited MUC16-specific serum IgG, although titers were higher in mice vaccinated with MUC16-coupled VLP on alum as compared to L1-MUC16 DNA vaccination. Antibody responses to mMUC16-targeted vaccination cross-reacted with hMUC16 peptide, and vice versa; both were reactive with the surface of CA125+ OVCAR3 cells, but not SKOV3 that lack detectable CA125 expression. Interestingly, vaccination of mice with mMUC16 peptide mixed with VLP and alum elicited mMUC16-specific IgG, implying VLPs provide robust T help and that coupling may not be required to break tolerance to this epitope. Conclusion: Vaccination with VLP displaying the 20 aa juxta-membrane MUC16 ectodomain, which includes the membrane proximal cleavage site, is likely to be well tolerated and induce IgG targeting ovarian cancer cells, even after CA125 is shed. [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]

BACKGROUND: For lung cancer, circulating tumor markers (TM) are available to guide clinical treatment decisions. To ensure adequate accuracy, pre-analytical instabilities need to be known and addressed in the pre-analytical laboratory protocols. OBJECTIVE: This study investigates the pre-analytical stability of CA125, CEA, CYFRA 21.1, HE4 and NSE for the following pre-analytical variables and procedures; i) whole blood stability, ii) serum freeze-thaw cycles, iii) electric vibration mixing and iv) serum storage at different temperatures. METHODS: Left-over patient samples were used and for every investigated variable six patient samples were used and analysed in duplicate. Acceptance criteria were based on analytical performance specifications based on biological variation and significant differences with baseline. RESULTS: Whole blood was stable for at least 6 hours for all TM except for NSE. Two freeze-thaw cycles were acceptable for all TM except CYFRA 21.1. Electric vibration mixing was allowed for all TM except for CYFRA 21.1. Serum stability at 4°C was 7 days for CEA, CA125, CYFRA 21.1 and HE4 and 4 hours for NSE. CONCLUSIONS: Critical pre-analytical processing step conditions were identified that, if not taken into account, will result in reporting of erroneous TM results. [ABSTRACT FROM AUTHOR]