Elevated Colonic Mucin Expression Correlates with Extended Time to Surgery for Ulcerative Colitis Patients

Area of Science:

• Gastroenterology
• Molecular Biology
• Genomics

Background:

• Ulcerative colitis (UC) pathogenesis involves genetic and environmental factors.
• Evidence suggests UC comprises multiple disease subclasses with differential treatment responses.
• Molecular subtyping via colonic transcriptome profiling offers a novel approach to classify UC.

Purpose of the Study:

• To molecularly subtype ulcerative colitis (UC) using transcriptomic data.
• To identify distinct molecular signatures within UC patient colonic tissues.
• To explore potential correlations between molecular subtypes and clinical outcomes.

Main Methods:

• RNA-sequencing (RNA-seq) performed on colonic tissues from 26 UC patients.
• Hierarchical clustering applied to transcriptomic data to identify disease subsets.
• Differential gene expression, cell type deconvolution, and network analyses used for subset characterization.

Main Results:

• Two distinct UC molecular subsets identified, differentiated by 957 genes.
• Cluster 1 showed enrichment in intestinal epithelial cell (IEC) differentiation genes.
• Cluster 2 exhibited enrichment in epithelial-to-mesenchymal transition (EMT) and inflammatory response genes.
• Cluster 1 associated with longer time from diagnosis to colectomy (HR=0.45, p=0.03).
• Elevated MUC5B, MUC4, and MUC2 expression in Cluster 1 correlated with prolonged time to surgery (HR=0.37, p=0.0044).

Conclusions:

• Transcriptome analysis reveals at least two distinct molecular signatures in UC.
• Elevated mucin gene expression (MUC5B, MUC4, MUC2) is linked to a longer time to colectomy.
• These mucin genes may serve as prognostic indicators for UC disease severity and progression.