CIRCULATING MICRORNAS AS NOVEL BIOMARKERS IN GYNECOLOGICAL CANCERS: CURRENT EVIDENCE AND FUTURE DIRECTION

Abstract

Gynecological cancers, including ovarian, cervical, and endometrial malignancies, remain leading causes of morbidity and mortality among women worldwide. Early detection and accurate prognostication are critical for improving clinical outcomes, yet current diagnostic tools often lack the sensitivity and specificity required for timely intervention. In this context, circulating microRNAs (miRNAs), small non-coding RNA molecules detectable in blood and other body fluids, have emerged as promising minimally invasive biomarkers. Their remarkable stability, reproducibility, and disease-specific expression patterns make them suitable candidates for both diagnostic and prognostic applications in gynecological oncology.

Recent studies have demonstrated that specific circulating miRNAs, such as miR-21, miR-200 family, and miR-125b, are consistently dysregulated in gynecological cancers and may distinguish malignant from benign conditions. These miRNAs regulate key oncogenic pathways, including cell proliferation, apoptosis, and metastasis, thereby linking their expression with disease progression and therapeutic resistance. Furthermore, circulating miRNAs have shown potential as predictive biomarkers for treatment response, particularly in ovarian and cervical cancers where chemotherapy resistance remains a major clinical challenge.

Technological advances, including next-generation sequencing and quantitative PCR platforms, have enhanced the sensitivity of miRNA profiling. However, challenges persist in translating these findings into clinical practice. Issues such as lack of standardized protocols, variability in sample processing, and limited reproducibility across cohorts hinder clinical validation. Additionally, most available data derive from small-scale or single-center studies, underscoring the need for large multicenter trials to establish robust miRNA signatures.

Looking forward, integration of circulating miRNA profiling with multi-omics approaches and machine learning algorithms may enable the development of comprehensive biomarker panels for early detection, prognosis, and personalized therapy. As evidence continues to grow, circulating miRNAs are poised to transform the clinical management of gynecological cancers by offering non-invasive, cost-effective, and reliable diagnostic and prognostic tools.