Exosomal MicroRNAs as Epigenetic Biomarkers for Endometriosis: A Systematic Review and Bioinformatics Analysis

The clinical application of exosomal microRNAs as diagnostic biomarkers presents a promising approach for identifying potential markers of endometriosis. We conducted a systematic review of case-control studies to investigate exosomal microRNAs as epigenetic biomarkers potentially involved in the pathogenesis of endometriosis. A comprehensive literature search was performed across PubMed, Embase, Web of Science, and Scopus databases, yielding 702 studies, with 12 meeting the inclusion criteria after screening and full-text review. These studies included 191 women with confirmed endometriosis and 169 healthy controls. Quality assessment using the Newcastle-Ottawa Scale indicated a moderate quality across studies, with a common score of 5/9. In total, 668 exosomal microRNAs were found to be significantly differentially expressed between endometriosis patients and controls. In serum samples, 119 exosomal microRNAs were differentially expressed, with miR-22-3p, miR-320a, miR-320b, and miR-1273g-3p reported in more than one study. In endometrial tissue samples, miR-200c-3p and miR-425-5p were identified in more than one study, with miR-200c-3p consistently upregulated. Bioinformatic analysis indicated that these exosomal microRNAs are involved in key signaling pathways such as PI3K/Akt, MAPK, and TGF-β, which are associated with cell proliferation, migration, and inflammation. Despite these promising findings, variability in exosomal microRNA expression patterns across studies underscores the need for standardized methods and validation in large-scale, ethnically diverse cohorts. Future research should focus on rigorous validation studies to establish clinically relevant exosomal microRNAs for early diagnosis and improved patient outcomes.