Elucidating the role of T-cell exhaustion-related genes in colorectal cancer: a single-cell bioinformatics perspective.

ABSTRACT

Colorectal cancer (CRC) remains a significant global health issue. In this study, the role of T-cell exhaustion-related genes (TEXs) in CRC was investigated using single-cell and bulk RNA-seq analysis. This research involved extensive data analysis using multiple databases, including the TCGA-COAD cohort, GSE14333, and GSE39582. Through single-cell analysis, distinct cell populations within CRC samples were identified and classified T-cells into four subgroups regulatory T-cells (Tregs), conventional CD4+ T-cells (CD4+ T conv), CD8+ T, and CD8+ T exhausted cells. Intercellular communication networks and signaling pathways associated with TEXs using computational tools such as CellChat and PROGENy. Additionally, TEX-related alterations in tumor gene pathways were analyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Prognostic models were developed, and their correlation with immune infiltration was assessed. The study revealed the presence of distinct cell populations within CRC, with TEXs playing a crucial role in the tumor microenvironment. CD8+ T exhausted cells exhibited expression of specific markers, indicating their involvement in tumor immune evasion. CellChat and PROGENy analyses revealed intricate communication networks and signaling pathways associated with TEXs, including RNA splicing and viral carcinogenesis. Furthermore, the prognostic risk model developed on the basis of TEXs demonstrated its efficacy in stratifying CRC patients. This risk model exhibited strong correlations with immune infiltration by various effector immune cells, highlighting the influence of TEXs on the tumor immune response. The complex interactions and signaling pathways underlying TEX-associated immune dysregulation in CRC were revealed by employing advanced analytical approaches. The development of a prognostic risk model based on TEXs offers a promising tool for prognostic stratification in patients with CRC. Furthermore, the correlations observed between TEXs and immune infiltration provide valuable insights into the potential of TEXs as therapeutic targets and highlight the need for further investigation into TEX-mediated immune evasion mechanisms. This study thus provides valuable insights into the role of TEXs in CRC.