Colonic Mucosal Transcriptomic Changes in Patients with Long-Duration Ulcerative Colitis Revealed Colitis-Associated...

Area of Science:

• Gastroenterology
• Molecular Biology
• Oncology

Background:

• Patients with long-standing ulcerative colitis (UC) face an elevated risk of developing colitis-associated cancer (CAC).
• Understanding the molecular underpinnings of this increased risk is crucial for early detection and prevention strategies.

Purpose of the Study:

• To identify transcriptomic differences between patients with long-duration UC (≥20 years) and short-duration UC (≤5 years).
• To explore the role of gene expression and alternative splicing in the context of UC disease duration.

Main Methods:

• Transcriptome profiling was performed on colonic biopsies from 32 UC patients (11 long-duration, 21 short-duration) using Affymetrix Human Transcriptome Array 2.0.
• Differential gene expression and alternative splicing events were analyzed, followed by KEGG and GO pathway analysis.
• Key findings were validated using quantitative PCR (qPCR).

Main Results:

• 640 differentially expressed genes were identified between the two groups, including notable up- and down-regulated genes.
• Significant alterations in metabolic pathways, fatty acid degradation, and bile secretion were observed, previously linked to CAC.
• 3560 genes showed differential alternative splicing, with 374 also exhibiting differential expression, highlighting the interplay between gene expression and splicing.

Conclusions:

• Long-duration UC is characterized by distinct alterations in gene expression, pathway activation, and alternative splicing events compared to short-duration UC.
• These transcriptomic changes offer potential biomarkers and insights into the pathogenesis of CAC in UC patients.