Comparative evaluation of the diagnostic value of microRNAs for early colorectal cancer detection in adults: Results of a systematic review and network meta-analysis.

Abstract

e15530 Background: Circulating microRNAs (miRNAs) are promising non-invasive biomarkers for colorectal cancer (CRC), but their diagnostic performance has not been systematically compared across a broad spectrum of miRNAs. This network meta-analysis evaluated the diagnostic potential of circulating miRNAs and their panels for early CRC detection. Methods: A systematic review and network meta-analysis were conducted (PROSPERO CRD420251062003). PubMed and Embase were searched, including studies published from 2000–2025. Histologically confirmed CRC patients and healthy controls were eligible. The primary outcome was AUC. Risk of bias was assessed using QUADAS-2. Statistical analyses were performed in R. Results: Forty-eight studies (69 miRNAs/panels) were included. MiR-155 and MiR-182 served as reference markers. Funnel plots indicated substantial publication bias. Heterogeneity was significant (I²=74.8% [53.0–86.5]; Q=35.7, p<0.001). No miRNA showed statistically significant benefit over references. SUCRA ranking identified three miRNA-21-based panels and two standalone candidates among the top five tools. Conclusions: This network meta-analysis provides the most comprehensive comparative evaluation of circulating miRNAs for early CRC detection. The combination miRNA-21 + miRNA-25 + miRNA-18a + miRNA-22 demonstrated the highest diagnostic potential and represents a promising candidate for non-invasive clinical implementation. Further clinical applicability will be clarified by pooled sensitivity and specificity analyses. Top five circulating miRNAs/miRNA panels by SUCRA ranking. miRNA Pooled AUC SUCRA score 21 + 25 + 18a + 22 0.93 [0.88; 0.96] 0.889 21 + 92a + 221 0.89 [0.78; 0.95] 0.799 21 + 221 + 150 0.82 [0.74; 0.88] 0.797 760 0.92 [0.83; 0.97] 0.774 221 0.81 [0.67; 0.90] 0.754