Identification of Immune-Related Genes in Predicting the Progression of Colitis-Associated Colorectal Cancer: An...

Immune infiltration plays an important role in the pathogenesis of both ulcerative colitis (UC) and colorectal cancer (CRC). Our aim is to explore the significance of immune cell-related genes in colitis-associated colorectal cancer (CAC).

Datasets related to UC and CRC were sourced from public databases. Key immune cell-related CAC genes (IC-CACs) were obtained by using WGCNA, differential expression and elastic net logistic regression analyses. Their diagnostic performance was assessed via ROC curves. Single-cell RNA sequencing (scRNA-seq) data were analyzed using the AUCell algorithm. Prognostic signatures were developed from differentially expressed genes between AUCell score-high and -low groups using Cox and LASSO regression. Moreover, the expressions of IC-CACGs were examined by RT-qPCR using clinical samples.

We obtained 13 key IC-CACGs correlated with neutrophils and dendritic cells. ROC curves revealed that key IC-CACGs had the good ability to distinguish UC or CRC patients from controls. scRNA-seq analysis revealed enrichment of interferon response, inflammation, and PI3K-Akt-mTOR signaling in AUCell scorehigh groups, while glycolysis and EMT were enriched in scorelow groups. A 20-gene prognostic signature was constructed and validated, with low-risk patients showing better overall survival. Key IC-CACGs correlated strongly with prognostic genes, and high-risk patients exhibited higher TIDE scores, suggesting poorer immunotherapy response. CD69, CXCR4, and SAMSN1 were highly expressed in T cells and natural killer T cells, and their expressions were significantly increased in CAC samples.

Our results provide the evidence for the promising role of immune cell-related genes in the development of CAC and new ideas for CAC prevention and treatment.