Evaluating MiRNAs in Blood-Based Liquid Biopsy for Early-Onset Colorectal Cancer Detection: A Systematic Review and Meta-Analysis

Background: A significant rise is observed in the incidence of early-onset colorectal cancer (EOCRC) worldwide, demanding discovery of promising non-invasive diagnostic biomarkers. This systematic review and meta-analysis evaluated the diagnostic accuracy of single circulating microRNAs (miRNAs) for EOCRC detection. Methods: The protocol for this systematic review was prospectively registered with PROSPERO (registration number: CRD420251252155). We systematically searched PubMed, Embase, Web of Science and Scopus through September 2025 following PRISMA 2020 guidelines. Studies stating diagnostic accuracy of single circulating miRNAs in blood samples for histologically confirmed CRC were included. The quality assessment of included studies was done by using QUADAS-2 and bivariate random-effect meta-analysis was performed to calculate pooled diagnostic metrics. Results: Sixteen studies comprising 909 CRC cases and 1214 controls evaluating 22 distinct miRNAs were included. In the primary meta-analysis restricted to early-onset colorectal cancer (EOCRC,