Diagnostic Potential of Cross-Specimen microRNA Panels as Biomarkers for Colorectal Cancer: A Systematic Review and...

Colorectal cancer remains a major global health challenge, necessitating the development of accurate non-invasive diagnostic tools. Circulating and excretory microRNAs (miRNAs) are promising biomarkers owing to their stability and regulatory roles in tumorigenic pathways. While single miRNA assays often lack sufficient diagnostic accuracy, panels combining multiple miRNAs have shown enhanced performance. This systematic review and meta-analysis evaluated the diagnostic accuracy of multi-miRNA panels and explored their mechanistic relevance to colorectal cancer pathogenesis.

A comprehensive search of PubMed, Embase, Web of Science, and Scopus was conducted through March 2025 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The study protocol was registered with PROSPERO (CRD420251060655). Eligible studies assessed the diagnostic accuracy of multi-miRNA panels for colorectal cancer using extractable data on sensitivity, specificity, and area under the curve. Data were extracted independently by two reviewers. A bivariate random-effects model was used to calculate pooled diagnostic estimates. Study quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool, and heterogeneity was evaluated using I² statistics. Subgroup analyses were conducted by sample type (e.g., plasma, serum, stool) and panel size. Target genes of recurrent miRNAs were mapped to canonical colorectal cancer-related pathways.

Twenty-nine studies comprising 5497 participants (3070 colorectal cancer cases and 2427 controls) and 35 multi-miRNA panels were included. Pooled sensitivity was 0.85 (95% confidence interval 0.80-0.88), specificity was 0.84 (95% confidence interval 0.80-0.88), and the area under the curve was 0.90, despite substantial heterogeneity (I² > 77%). Panels derived from plasma samples showed the highest balanced performance (sensitivity 0.88; specificity 0.87), while three-miRNA panels exhibited the best diagnostic trade-offs. Mechanistic analysis of 42 recurrent miRNAs revealed consistent involvement in key colorectal cancer pathways, including PI3K/AKT, Wnt/β-catenin, epithelial-mesenchymal transition, angiogenesis, and immune regulation.

Multi-miRNA panels derived from diverse biospecimen sources demonstrate high diagnostic accuracy for colorectal cancer and are mechanistically linked to fundamental oncogenic pathways. Future efforts should focus on panel standardization, biospecimen-specific validation, and integration into clinical workflows to advance precision oncology.