Circulating potential biomarkers in polycystic ovary syndrome and gynecologic cancers: Diagnostic insights from a systematic review and meta-analysis

Abstract

Background: Epidemiological evidence indicates a higher risk of endometrial cancer (EC) and ovarian cancer (OC) in females suffering from Polycystic Ovary Syndrome (PCOS), highlighting that these disease groups might be sharing common molecular pathogenesis mechanisms. This systematic review and meta-analysis evaluated the unique and common liquid biopsy-based markers for their diagnostic potential as well as their role in the pathogenesis of PCOS, EC, and OC. Methods: A systematic search was conducted across PubMed and Embase databases to identify studies investigating circulating markers, including microRNAs, long non-coding RNAs, circular RNAs, and other non-coding RNAs for their diagnostic potential in PCOS, EC, and OC. A total of 46 studies for PCOS, 27 studies for EC, and 91 studies for OC met the eligibility criteria. Data on diagnostic performance, including area under the curve (AUC with 95% CI), sample size, sensitivity, and specificity, were synthesized from eligible studies, and meta-analysis was performed where feasible. Results: A wide array of markers was listed along with their diagnostic potential across these disorders. miR-222-3p, miR-4488, and miR-151-5p performed well in PCOS, miR-27a, miR-145, miR-150-5p in EC, and miR-21, miR-1246, miR-193a-5p, miR-200a, circBNC2 and circFOXP1 in OC. Pooled meta-analysis showed promising AUC values for miR-21 (0.81), miR-200a (0.86), miR-200b (0.84), and miR-200c (0.79) in OC, underscoring their strong diagnostic potential. For PCOS and EC, only two studies each were available for miR-223-3p and miR-27a, respectively. In subgroup analysis, miR-21 (0.81), miR-200c (0.78), miR-145 (0.89), and miR-27a (0.75) showed the highest diagnostic performance, but with high heterogeneity and a non-significant subgroup effect. Conclusion: Circulating RNAs offer significant diagnostic, prognostic, and risk-stratification potential for PCOS and gynecologic cancers; however, standardized methodologies and large, independent, diverse cohort studies are needed to validate these findings and optimize clinical translation. Trial Registration: PROSPERO (CRD42024573106)