Biopsy-Based Molecular Signatures Predicting Therapeutic Response in Ulcerative Colitis
- 1Histopathology Unit, National Institute of Gastroenterology—IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy
- 2IBD Unit, National Institute of Gastroenterology—IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy
Abstract
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.
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BibTeX
@article{grassi2026biopsybased,
title = {{Biopsy-Based Molecular Signatures Predicting Therapeutic Response in Ulcerative Colitis}},
author = {Ilaria Grassi and Marina Liso and Mauro Mastronardi and Anna Maria Valentini and Margherita Curlo and Raffaele Armentano and Elisabetta Cavalcanti},
journal = {International journal of molecular sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27198838},
url = {https://europepmc.org/article/PMC/PMC13664742},
note = {CC BY},
}
RIS
TY - JOUR
TI - Biopsy-Based Molecular Signatures Predicting Therapeutic Response in Ulcerative Colitis
AU - Ilaria Grassi
AU - Marina Liso
AU - Mauro Mastronardi
AU - Anna Maria Valentini
AU - Margherita Curlo
AU - Raffaele Armentano
AU - Elisabetta Cavalcanti
PY - 2026
DA - 2026/10/01
JO - International journal of molecular sciences
DO - 10.3390/ijms27198838
UR - https://europepmc.org/article/PMC/PMC13664742
AB - 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.
SN - 1422-0067
ER -