Circulating microRNAs as Diagnostic Biomarkers to Detect Specific Stages of Ovarian Cancer: A Comprehensive Meta-Analysis

Background: Ovarian cancer (OC) remains the deadliest gynecological malignancy, despite significant treatment advances. The absence of early detection tests results in advanced-stage diagnosis for 70% of OC cases. MicroRNAs (miRNAs) are known to be dysregulated in OC. Their presence or absence in circulation may indicate malignancy, potentially before tumor formation or metastasis. We hypothesize that miRNA expression patterns shift with OC progression and could facilitate stage-specific detection. Methods: We searched Pubmed, Embase, and Web of Science, and a total of 50 articles with 209 studies and 11,158 participants were included. We assessed the utility of circulating miRNAs for detecting OC, particularly at different stages, using the bivariate hierarchical random-effects model. Results: Using this model, the panels of miRNAs (83.92% sensitivity and 89.82% specificity) performed significantly better than single miRNAs (76.91% sensitivity and 70.56% specificity). Combining miRNA panels with the classical biomarkers, cancer antigen-125 and/or human epididymis protein significantly improved the detection to 93.39% sensitivity and 92.71% specificity. miR-200c, miR-1246, miR-141, miR-200b, miR-200a, and miR-429 are among the miRNA species with sensitivity and specificity greater than 70%. miR-141, miR-320b, miR-223, and miR-200c were frequently used to identify early-stage OC, showing 84.78% sensitivity and 82.37% specificity. For late-stage OC, miR-200c, miR141, miR-1246, and miR-320b were the frequent miRNAs used, providing 79.97% sensitivity and 81.97% specificity. While patient demographics and detection methods influence the variability in the diagnostic accuracy of miRNAs, factors such as the control types (healthy individuals or benign growths), the directions of level changes (upregulated and downregulated), and the sample sizes did not impact the diagnostic precision. Conclusion: This study highlights the utility of circulating miRNAs for OC detection at specific stages, enabling the development of minimally invasive early detection tests and allowing stage-specific approaches for more personalized and precise therapeutic management.