Abstract
<title>Abstract</title> <p> Early detection of colorectal cancer (CRC) significantly improves clinical outcomes; however, the widely used faecal immunochemical test (FIT) exhibits suboptimal sensitivity. We aimed to develop a blood-based diagnostic panel using high-mannose (HM)-associated miRNAs captured by recombinant <italic>Oscillatoria agardhii</italic> agglutinin (OAA1). Using a two-stage design, we analysed retrospective discovery (n = 99) and prospective validation (n = 21) cohorts. Serum HM-associated miRNAs were captured using OAA1-immobilised columns and quantified using reverse transcription-quantitative polymerase chain reaction. Stepwise multivariate logistic regression identified an optimised 4-miRNA panel (miR-122-5p, miR-130a-3p, miR-15b-5p, and miR-126-3p) with an area under the curve (AUC) of 0.886 in the discovery cohort. The panel score exhibited a significant stage-dependent increasing trend across the adenoma-carcinoma sequence (P < 0.0001) and was independent of tumour location, maximum tumour diameter, and conventional tumour markers. In the independent validation cohort, this panel achieved an AUC of 0.944, with 83.33% sensitivity and 100% specificity. These results suggest that the OAA1-captured 4-miRNA panel can serve as a specific, non-invasive liquid biopsy tool for early CRC detection. This may help address the anatomical and tumour burden limitations of the FIT, suggesting its potential utility as a secondary screening strategy in clinical practice. </p>