A Seven-NF-κB-Related Gene Signature May Distinguish Patients with Ulcerative Colitis-Associated Colorectal Carcinoma

Area of Science:

• Oncology
• Gastroenterology
• Molecular Biology

Background:

• Ulcerative colitis (UC) patients face a higher risk of colorectal cancer (CRC).
• Ulcerative colitis-associated colorectal cancer (CAC) is more aggressive and has a worse prognosis than sporadic CRC.
• Predictive biomarkers are needed for early detection of CAC in UC patients in remission.

Purpose of the Study:

• To identify a gene signature for predicting CAC risk in UC patients during remission.
• To investigate the molecular pathways involved in UC-associated tumorigenesis.

Main Methods:

• Analysis of UC transcriptome data from the Gene Expression Omnibus (GEO) database.
• Utilized Gene Set Variation Analysis (GSVA), Gene Set Enrichment Analysis (GSEA), and Weighted Correlation Network Analysis (WGCNA) with protein-protein interaction (PPI) analysis.
• Developed a predictive model using a generalized linear model (GLM) of Poisson regression.

Main Results:

• The tumor necrosis factor (TNF) signaling via NF-κB pathway was significantly upregulated.
• A seven-gene signature (FOS, CCL4, CXCL1, MYC, CEBPB, ATF3, JUNB) related to NF-κB was identified with higher expression in CAC.
• The seven-gene signature demonstrated a diagnostic value with an AUC of 0.82 in the validation cohort.

Conclusions:

• The identified seven-gene NF-κB-related signature can serve as a predictive index for tumorigenesis in UC patients in remission.
• This gene signature holds potential for early risk assessment of CAC in UC patients.
• Further validation may lead to clinical application for improved patient management.