Serum miR-200c-3p and -6134 as Biomarkers for Epithelial Ovarian Cancer: A Comprehensive analsis with CA125

Background: MicroRNAs (miRNAs) regulate gene expression in epithelial ovarian cancer (EOC). In a single-center, retrospective study, we aimed to assess serum miRNAs as EOC biomarkers, and whether combined miRNAs and cancer antigen (CA)125 discriminated EOC from benign ovarian tumors. Results: Sera were collected from patients with EOC (N=95) or benign ovarian tumors (N=115), and from healthy controls (N=40). Candidate serum miRNAs were screened by miRNA microarray and quantified by real-time reverse transcription (RT)-PCR. Serum CA125 was measured by enzyme-linked immunosorbent assay. Real-time RT-PCR revealed highly expressed miR-200c-3p and -6134 in EOC. These miRNAs and CA125 correlated with disease severity and histological classification. In EOC vs. healthy controls, miR-200c-3p and -6134 were significantly upregulated; the area under the curve (AUC)=0.693 (95% confidence interval [CI]: 0.606–0.780) and 0.818 (0.749–0.888), respectively. Levels of miR-200c-3p, -6134, and CA125 were significantly upregulated in EOC vs. benign ovarian tumors; AUC=0.848 (95% CI: 0.792–0.904), 0.933 (95% CI: 0.891–0.975), and 0.811 (95% CI: 0.752–0.871), respectively. Combined with CA125, the two miRNAs showed AUC=0.907 (95% CI: 0.855–0.959) in normal vs. EOC and 0.952 (95% CI, 0.919–0.985) in benign tumors vs. EOC. For combined miR-200c-3p and -6134, AUC=0.935 (CA125 < 35 U/mL) and 0.934 (CA125 ≥ 35 U/mL). Conclusions: For CA125 < 35 U/mL, combined miR-200c-3p and miR-6134 distinguished EOC from benign ovarian tumors with high discriminative power. Combining two miRNAs with CA125 improved diagnostic accuracy, highlighting the potential of miR-200c-3p and -6134 as ancillary markers for detecting EOC, especially in cases with normal CA125 levels.