Biopsy-Based Molecular Signatures Predicting Therapeutic Response in Ulcerative Colitis

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with marked molecular heterogeneity, resulting in highly variable responses to biologic therapies. Despite the efficacy of Infliximab (IFX), many patients fail to achieve sustained remission. Identifying biomarkers predictive of treatment response is essential for advancing precision medicine in UC. Gene expression profiling of colonic mucosal biopsies from IFX responders, IFX non-responders, and healthy controls was performed using a multiplex array, followed by technical confirmation by RT-qPCR and immunohistochemical assessment to further characterize tissue expression and biological relevance. IFX non-responders displayed a stromal-immune molecular signature marked by extracellular matrix remodeling, stromal remodeling, integrin-mediated signaling, and persistent inflammatory pathways. SPARC and SPP1 emerged as the most prominent biomarkers, with significantly increased gene and protein expression in non-responder patients, highlighting their association with chronic tissue remodeling and therapeutic resistance. Mucosal resistance to IFX is associated with a specific stromal-immune profile characterized by SPARC and SPP1 upregulation. These findings suggest that both molecules may serve as promising candidate markers for patient stratification, highlighting the need for future prospective studies to explore their role in personalized management strategies for ulcerative colitis.