Elucidating the role of T-cell exhaustion-related genes in colorectal cancer: a single-cell bioinformatics perspective.
Bioinformatics
Colorectal cancer
Prognostic risk model
Single-cell analysis
Tumor immune microenvironment
Journal
Functional & integrative genomics
ISSN: 1438-7948
Titre abrégé: Funct Integr Genomics
Pays: Germany
ID NLM: 100939343
Informations de publication
Date de publication:
02 Aug 2023
02 Aug 2023
Historique:
received:
21
06
2023
accepted:
26
07
2023
revised:
23
07
2023
medline:
3
8
2023
pubmed:
2
8
2023
entrez:
1
8
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37528306
doi: 10.1007/s10142-023-01188-9
pii: 10.1007/s10142-023-01188-9
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
259Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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