Dataset Information

CA125-Tn ELISA assay improves specificity of pre-operative diagnosis of ovarian cancer among patients with elevated serum CA125 levels.

ABSTRACT:

Background

CA125 is the most widely used serum marker for preoperative diagnosis of ovarian cancer. However, CA125 elevation is not specific to ovarian cancer. More than 60% of patients who have elevated CA125 levels do not have ovarian cancer. To overcome the low specificity of CA125, we identified a CA125 glycoform that was specifically elevated in ovarian cancer and that may help in the further triage of patients with elevated serum CA125 levels.

Methods

We used antibody-lectin ELISA to detect various CA125 glycoforms. Among 21 lectins tested, VVA, a plant lectin that preferentially binds Tn antigen, showed significantly stronger binding with ovarian cancer-derived CA125 than benign condition-derived CA125. CA125-Tn levels were tested among patients with elevated CA125 levels (n=328, including 68 ovarian cancer, 15 ovarian borderline tumors, and 245 benign conditions). The efficacy of CA125-Tn in diagnosing ovarian cancer was evaluated using ROC analysis.

Results

Medians and 25^th to 75^th quartiles of CA125-Tn levels were 0.31 (0.18-0.65) in ovarian cancer, 0.07 (0.02-0.12) in ovarian borderline tumor, and 0.07 (0.01-0.12) in benign conditions. AUC of the ROC curve was 0.890 (95% CI: 0.845, 0.935) for CA125-Tn to discriminate ovarian cancer cases from nonmalignant cases (borderline tumors and benign conditions). Its performance was even better among patients older than 45 y (AUC: 0.905, 95% CI: 0.841, 0.969). Specificity was improved from 35.1% for CA125 to 75.7% for CA125-Tn among patients older than 45 y when sensitivity was fixed at 90%.

Conclusions

CA125-Tn ELISA assay can improve specificity of the preoperative diagnosis of ovarian cancer and serve as a further triage strategy for patients with elevated CA125 levels.

SUBMITTER: Wang YS

PROVIDER: S-EPMC8246179 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Publications

CA125-Tn ELISA assay improves specificity of pre-operative diagnosis of ovarian cancer among patients with elevated serum CA125 levels.

Wang Yi-Sheng YS Ren Shi-Fang SF Jiang Wei W Lu Jia-Qi JQ Zhang Xiao-Yan XY Li Xiao-Ping XP Cao Rui R Xu Cong-Jian CJ

Annals of translational medicine 20210501 9

<h4>Background</h4>CA125 is the most widely used serum marker for preoperative diagnosis of ovarian cancer. However, CA125 elevation is not specific to ovarian cancer. More than 60% of patients who have elevated CA125 levels do not have ovarian cancer. To overcome the low specificity of CA125, we identified a CA125 glycoform that was specifically elevated in ovarian cancer and that may help in the further triage of patients with elevated serum CA125 levels.<h4>Methods</h4>We used antibody-lectin ...[more]

PMID: 34268401

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Project description:ObjectiveSurvival in epithelial ovarian cancer (EOC) remains poor. Most patients are diagnosed in late stages. Early diagnosis increases the chance of survival. We used the proximity extension assay from Olink Proteomics to search for new protein biomarkers with the potential to improve the diagnostic performance of CA125 and HE4 in patients with ovarian tumors.Material and methodsPlasma samples were obtained from 180 women with ovarian tumors; 30 cases of benign tumor, 28 cases with borderline tumors, 25 early EOC cases (FIGO stage I) and 97 advanced EOC cases (FIGO stages II-IV). Proteins were measured using the Olink® Oncology II and Inflammation panels. For statistical analyses, patients were categorized into benign tumors versus cancer and benign tumors versus borderline + cancer, respectively.ResultsWe analyzed 177 biomarkers. Thirty-four proteins had ROC AUC > 0.7 for discrimination between benign tumors and cancer. Fifteen proteins had ROC AUC > 0.7 for discrimination between benign tumors and borderline tumors + cancer. HE4 ranked highest for both comparisons. A reference model with HE4, CA125 and age (AUC 0.838 for benign tumors vs. cancer and AUC 0.770 for benign tumors vs. borderline tumors + cancer) was compared to the reference model with the addition of each of the remaining proteins with AUC > 0.7. ITGAV was the only individual biomarker found to improve diagnostic performance of the reference model, to AUC 0.874 for benign tumors vs. cancer and AUC 0.818 for benign tumors vs. borderline tumors + cancer (p < 0.05). Cross-validation and LASSO regression was combined to select multiple biomarker combinations. The best performing model for discrimination between benign tumors and borderline tumors + cancer was a 6-biomarker combination (HE4, CA125, ITGAV, CXCL1, CEACAM1, IL-10RB) and age (AUC 0.868, sensitivity 0.86 and specificity 0.82, p = 0.016 for comparison with the reference model).ConclusionHE4 was the best performing individual biomarker for discrimination between benign ovarian tumors and EOC including borderline tumors. The addition of other carcinogenesis-related biomarkers in a multiplex biomarker panel can improve the diagnostic performance of the established biomarkers HE4 and CA125.

Project description:BackgroundOvarian cancer (OC) is a highly aggressive gynecological malignancy prevalent worldwide. Most OC cases are typically diagnosed at advanced stages, which has led to a 5-year overall survival rate of less than 35% following conventional treatment. Furthermore, immune checkpoint inhibitor therapy has shown limited efficacy in the treatment of patients with OC, and CAR-T therapy has also demonstrated modest results owing to inadequate T cell infiltration. Therefore, novel strategies must be developed to enhance T cell persistence and trafficking within the OC tumor microenvironment.MethodsIn this study, we developed a novel adoptive T-cell therapy for ovarian cancer based on a chimeric antigen receptor structure. We used a ligand-receptor binding motif to enhance the therapeutic effect of targeting CA125. Since mesothelin can naturally bind to CA125 with high affinity, we concatenated the core-binding fragment of mesothelin with the 4-1BB and CD3ζ signal fragments to assemble a novel CA125-targeting chimeric receptor (CR). The CAR structure targeting CA125 derived from the 4H11 antibody was also constructed. CR- and CAR-encoding RNA were electroporated into T cells to evaluate their antitumor activity both in vitro and in vivo.ResultsWhile CR-T or CAR-T cells exhibited moderate activity against two ovarian cancer cell lines, T cells co-expressing CR and CAR exhibited a superior killing effect compared to T cells expressing either CR or CAR alone. Furthermore, upon interaction with ovarian tumors, the ability of CR and CAR T cells to release activation markers and functional cytokines increased significantly. Similarly, CR and CAR co-expressing T cells persistently controlled the growth of transplanted ovarian cancer tumors in NSG mice and significantly prolonged the overall survival of tumor-challenged mice. Transcriptome sequencing revealed that the survival and cytotoxicity of T cells co-expressing CR and CAR were significantly altered compared with those of T cells expressing either CR or CAR.ConclusionOur findings demonstrate that CA125 targeting CR and CAR can synergistically kill ovarian cancer cells, indicating that CA125 targeting by the two binding motifs simultaneously in tumors may improve the therapeutic outcomes of ovarian cancer treatment.

Dataset Information

CA125-Tn ELISA assay improves specificity of pre-operative diagnosis of ovarian cancer among patients with elevated serum CA125 levels.

Background

Methods

Results

Conclusions

Publications

CA125-Tn ELISA assay improves specificity of pre-operative diagnosis of ovarian cancer among patients with elevated serum CA125 levels.

Similar Datasets

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