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Predictors of pretreatment CA125 at ovarian cancer diagnosis: a pooled analysis in the Ovarian Cancer Association Consortium.

ABSTRACT: PURPOSE:Cancer 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. METHODS:We 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. RESULTS:In 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. CONCLUSION:Our 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.

SUBMITTER: Babic A

PROVIDER: S-EPMC5593071 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Predictors of pretreatment CA125 at ovarian cancer diagnosis: a pooled analysis in the Ovarian Cancer Association Consortium.

Babic Ana A Cramer Daniel W DW Kelemen Linda E LE Köbel Martin M Steed Helen H Webb Penelope M PM Johnatty Sharon E SE deFazio Anna A Lambrechts Diether D Goodman Marc T MT Heitz Florian F Matsuo Keitaro K Hosono Satoyo S Karlan Beth Y BY Jensen Allan A Kjær Susanne K SK Goode Ellen L EL Pejovic Tanja T Moffitt Melissa M Høgdall Estrid E Høgdall Claus C McNeish Iain I Terry Kathryn L KL

Cancer causes & control : CCC 20170103 5

<h4>Purpose</h4>Cancer 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 infl ...[more]

PMID: 28050675

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Project description:BackgroundCA125 is a prevalently used serum biomarker for detecting ovarian cancer over the last three decades. However, it has a significant deficiency in screening for early-stage cancer. With the purpose of exploring an effective approach to improve its performance in early diagnosis, we investigated the postprandial fluctuation pattern of cancer-derived CA125 and the underlying mechanism.MethodsIn two medical centers, 551 patients sonographically diagnosed with ovarian (adnexal) cysts (< 5 cm in diameter) were enrolled and divided into five disease groups (pelvic inflammatory cysts, retention cysts, endometrioma, benign/borderline cystadenoma and malignant cysts). The subtle differences in 1-h postprandial serum CA125 increases were compared between disease groups. A support vector machine (SVM)-based algorithm was used for refining the performance of CA125 postprandial increment. Ovarian cancer xenograft animal and cancer cell models were used to recapitulate the clinical findings and reveal the molecular basis of postprandial blood glucose and insulin in invoking the synthesis/secretion/re-absorption of CA125.ResultsPatients with ovarian cancer presented the highest postprandial increment 13.3 ± 0.7% (mean ± standard deviation) among the five disease groups. Using a CA125 increment ≥ 10% criterion, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) reached 83.3, 96.3, 61.1 and 98.8%, respectively, for early-stage ovarian cancer. This performance was further improved by the SVM-based CA125-increment algorithm, which exhibited 91.7% sensitivity, 99.2% specificity, 89.2% PPV and 99.4% NPV. Both modalities manifested diagnostic advantages over the traditional CA125 test (75.0% sensitivity, 25.4% specificity, 6.6% PPV and 93.6% NPV at the cut-off of 35 U/mL). Regarding the molecular basis, the postprandial blood glucose and insulin-invoked overexpression of Mucin 16 (encoding CA125) were demonstrated in animal and cancer cell models, which were mediated by the PI3K-Akt pathway. Nevertheless, a Mesothelin-based CA125 re-absorption behavior was noted in the treated cancer cells, which contributed to the over-drop following the postprandial peak of serum CA125.ConclusionsCancer-derived serum CA125 possesses a unique and distinctive postprandial pattern, that distinguishes it from the common CA125 elevation in a benign disease condition. The dynamic measurement/assessment strategy can achieve a discriminatory power superior to that of a static test.

Dataset Information

Predictors of pretreatment CA125 at ovarian cancer diagnosis: a pooled analysis in the Ovarian Cancer Association Consortium.

Publications

Predictors of pretreatment CA125 at ovarian cancer diagnosis: a pooled analysis in the Ovarian Cancer Association Consortium.

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