Differential Serum MicroRNA Profiling in Benign and Malignant Ovarian Tumours: An Exploratory Study Identifying hsa-miR-200c-3p as a Candidate Diagnostic Biomarker

Background/Objectives: Preoperative discrimination of benign from malignant adnexal masses remains a major clinical challenge, and circulating microRNAs (miRNAs) are candidate non-invasive biomarkers. This exploratory, hypothesis-generating study—not a diagnostic validation study—evaluated serum hsa-miR-200c-3p as a candidate diagnostic biomarker for ovarian malignancy. Methods: Serum from 39 women with an adnexal mass and a surgical indication (20 benign, 19 malignant), all with histological confirmation, was analysed. Of 179 assayed miRNAs, 178 were tested for differential expression (miR-103a-3p as endogenous reference) using the Mann–Whitney U test with Benjamini–Hochberg false-discovery-rate (FDR) correction; hsa-miR-200c-3p, a pre-specified miR-200 family candidate, was evaluated by ROC analysis and compared with, and adjusted for, CA 125, HE4 and age. Results: The malignant group was substantially older and more frequently postmenopausal. Thirty-eight miRNAs were significant after FDR correction; hsa-miR-200c-3p was up-regulated in malignancy. In the complete-case analysis restricted to the 35 participants with a detectable marker (20 benign, 15 malignant), the AUC was 0.893 (95% CI 0.76–0.99); however, four high-grade serous carcinomas showed undetectable serum hsa-miR-200c-3p, and when these were included and imputed as low expression (all-case analysis, n = 39) the AUC fell to 0.705 (95% CI 0.51–0.88). hsa-miR-200c-3p did not demonstrate statistically superior performance to HE4 (AUC 0.93) or CA 125 (0.89), with overlapping confidence intervals; any incremental value beyond established markers and age was modest and exploratory. Conclusions: Serum hsa-miR-200c-3p is a preliminary candidate that requires prospective, age-matched, adequately powered validation with pre-specified assays and analysis plans.