Tissue MicroRNA Expression Signatures as Diagnostic Biomarkers and Predictors of Residual Disease Activity and Relapse in Treatment-Naïve Pediatric Inflammatory Bowel Disease

Identifying novel diagnostic and prognostic biomarkers for pediatric inflammatory bowel diseases (PIBD), including Crohn's disease (pCD) and ulcerative colitis (pUC), is essential for enhancing treatment outcomes. MicroRNAs (miRNAs) have been recognized for their broader relevance in PIBD pathogenesis. This study investigates their diagnostic potential and clinical utility in PIBD. This prospective, monocentric study, with retrospective validation, involved 119 PIBD patients (58 pCD, 61 pUC) and 39 non-IBD controls. Small RNA next-generation sequencing was performed on fresh-frozen gut biopsies, targeting histopathologically confirmed inflamed areas. Twenty-five dysregulated miRNA candidates were validated via RT-qPCR in formalin-fixed, paraffin-embedded gut biopsies. Logistic regression was used to establish diagnostic and prognostic miRNA expression signatures. A diagnostic signature of 5 miRNAs (miR-223-3p, miR-34a-5p, miR-194-5p, miR-215-5p, miR-338-3p) distinguished pCD from non-IBD with 96.49% accuracy. Two miRNAs (miR-223-3p, miR-194-5p) differentiated pUC from non-IBD with 100% accuracy, and miR-215-5p distinguished pCD from pUC specimens with 83.54% accuracy. For treatment-naïve pCD patients, 7 miRNAs predicted residual disease activity at 3 months with 100% accuracy. Additionally, a distinct signature predicted the risk of relapse within 12 months with an accuracy of 84.21%. In this study, we have established tissue miRNA expression signatures with significant diagnostic and prognostic potential for use in PIBD. These findings aid in stratifying disease severity and risk, paving the way for more precise and personalized management of pediatric IBD.