Pathways Related to Colon Inflammation Are Associated with Colorectal Carcinoma: A Transcriptome- and Methylome-Wide...

Area of Science:

• Gastroenterology and Oncology
• Molecular Biology
• Cancer Pathogenesis

Background:

• Chronic inflammation is a known driver of colorectal cancer (CRC) in ulcerative colitis (UC).
• The role of inflammation in sporadic CRC pathogenesis is less understood.
• Understanding inflammation's role in sporadic CRC is crucial for developing new therapies.

Purpose of the Study:

• To investigate the association between inflammatory pathway dysregulation and sporadic CRC.
• To identify specific metabolic and signaling pathways altered in sporadic CRC.
• To validate these findings in a larger, diverse patient cohort.

Main Methods:

• RNA-sequencing (RNA-seq) to identify gene-pathway changes in UC-associated CRC (n=10) as a proxy for inflammation.
• Analysis of sporadic CRC (n=8) for associations with identified inflammatory pathways.
• Replication study using microarray on a larger cohort of sporadic CRC patients (n=71).

Main Results:

• Down-regulation of inflammation-related metabolic pathways (nitrogen, sulfur metabolism) and bile secretion/fatty acid degradation pathways in sporadic CRC.
• Up-regulation of the proteasome pathway, unrelated to inflammation, was observed.
• Inflammation-CRC associations were significant and consistent across subgroups (sex, stage, grade, MSI, KRAS).

Conclusions:

• Inflammatory pathway dysregulations are associated with sporadic colorectal cancer pathogenesis.
• Specific metabolic pathways are altered in sporadic CRC, implicating inflammation.
• These findings suggest novel therapeutic targets for sporadic CRC treatment.