Beyond CA-125: circulating cell-free DNA as the next-generation biomarker in ovarian malignancy

Due to a lack of efficient screening methods or trustworthy biomarkers with high sensitivity and specificity, ovarian cancer (OC) is a quarrelsome disease with a high death rate. Investigators believe that circulating tumor cell-free DNA (cfDNA) can provide crucial clues concerning both primary and metastatic OCs. Our goal was to identify the potential of circulating cfDNA as a non-invasive biomarker for ovarian cancer.

This case‒control prospective study was carried out on 150 participants, of whom 50 patients were confirmed to have ovarian cancer, 50 patients had benign ovarian lesions, and 50 participants were controls. For OC patients, medical, laboratory, and imaging evaluations together with survival analysis were performed. Quantification of cfDNA was done by real-time PCR.

A distinct difference in the mean cfDNA was observed in the malignant group (11.84 ng/mL) compared to the benign (3.90 ng/mL) and control (0.23 ng/mL) groups. ROC curve analysis revealed that cfDNA had the highest value as a strong discriminatory marker for prediction of ovarian cancer in suspected cases and prediction of late stage and is a reasonable predictor of mortality (AUC 0.934, p < 0.001, 95% CI: 0.881-0.986; AUC 0.993, p < 0.001, 95% CI: 0.978-1.0; and AUC 0.814, p = 0.001, 95% CI: 0.690-0.937). The multivariate logistic regression reinforces its independent prognostic value for progression-free survival and overall survival.

Our results indicate that cfDNA has a strong correlation with tumor grade and predictive capability in Cox models, suggesting that it may serve as a diagnostic and prognostic biomarker for OC. In clinical setting, these findings support the use of cfDNA in OC risk stratification and treatment planning, potentially enabling aggressive therapies for patients with high cfDNA expression.