Circulating microRNAs and Endometriosis: A Comprehensive Analysis and Validation of Identified Biomarkers in the Indian Population

Abstract Endometriosis is a prevalent condition where tissue similar to the uterine lining grows outside the uterus, causing pain and infertility. Diagnosing endometriosis typically requires invasive procedures like laparoscopy. MicroRNAs (miRNAs) have emerged as promising non-invasive biomarkers for various diseases, including endometriosis. However, studies have shown inconsistent miRNA expression patterns across populations. This study aims to validate circulating miRNAs as biomarkers for endometriosis in Indian women, addressing the limited validation data available for this population. A comprehensive review identified nine circulating miRNAs based on reproducibility and consistent expression patterns. Women with advanced-stage endometriosis (n = 12) and controls (n = 11) were recruited. Plasma samples were collected based on clinical symptoms, CA-125 levels, ultrasound, MRI findings, and laparoscopic confirmation. miRNA expression was quantified using qRT-PCR, and Receiver Operating Characteristic (ROC) analysis was performed to assess diagnostic potential. Nine miRNAs (miR-451a, let-7b, miR-150-5p, miR-17-5p, miR-3613-5p, miR-20a-5p, miR-342-3p, miR-125b-5p, and miR-21-5p) were analyzed. Among them, miR-451a and miR-20a-5p exhibited significantly lower expression in endometriosis patients (n = 12) compared to controls (n = 11). ROC analysis demonstrated promising diagnostic potential for these miRNAs. miR-451a showed distinct trends compared to previous studies, while miR-20a-5p was consistent with earlier research. Although encouraging, these findings are based on a limited sample size. Larger, multi-center studies across diverse populations using reliable reference genes are needed to fully assess the diagnostic value of these miRNAs as biomarkers for endometriosis. Lay Summary Endometriosis is a common condition where tissue similar to the uterine lining grows outside the uterus, causing pain and infertility. Diagnosing it usually requires invasive procedures like laparoscopy. We focused on microRNAs (miRNAs), small molecules in plasma that could offer a noninvasive way to diagnose endometriosis. After reviewing 45 research articles, we identified 102 miRNAs that were elevated and 197 that were reduced in endometriosis patients. From these, we selected nine promising miRNAs for validation in the Indian population. We collected blood samples from 12 women with endometriosis and 11 healthy controls. Our analysis showed significant differences in miRNA expression, with miR-451a and miR-20a-5p showing strong potential to distinguish between endometriosis patients and healthy individuals. These findings suggest that miRNAs could improve the diagnosis of endometriosis in a less invasive manner. In conclusion, our research highlights the potential of miRNAs in advancing endometriosis diagnosis and management.