Immune-related genes in tumor-specific CD4+ and CD8+ T cells in colon cancer

BMC Cancer. 2020 Jun 22;20(1):585. doi: 10.1186/s12885-020-07075-x.

Abstract

Background: Immune escape is an immunological mechanism underlying tumorigenesis, and T cells play an important role in this process. In this study, immune-related genes were evaluated in tumor-infiltrating CD4+ and CD8+ T cells in colon cancer.

Methods: ESTIMATE was used to calculate stromal and immune scores for tumor datasets downloaded from The Cancer Genome Atlas-Colon Cancer (COAD). Differentially expressed genes (DEGs) between samples with high and low stromal and immune scores were screened, followed by a functional enrichment analysis of the overlapping DEGs. The DEGs related to CD4+ and the CD8+ T cells were then screened. Predicted miRNA-mRNA and lncRNA-miRNA pairs were used to construct a competing endogenous RNA (ceRNA) network. Furthermore, chemical-gene interactions were predicted for genes in the ceRNA network. Kaplan-Meier survival curves were also plotted.

Results: In total, 83 stromal-related DEGs (5 up-regulated and 78 down-regulated) and 1270 immune-related DEGs (807 up-regulated and 293 down-regulated genes) were detected. The 79 overlapping DEGs were enriched for 39 biological process terms. Furthermore, 79 CD4+ T cell-related genes and 8 CD8+ T cell-related genes, such as ELK3, were screened. Additionally, ADAD1 and DLG3, related to CD4+ T cells, were significantly associated with the prognosis of patients with colon cancer. The chr22-38_28785274-29,006,793.1-miR-106a-5p-DDHD1 and chr22-38_28785274-29,006,793.1-miR-4319-GRHL1 axes obtained from CD4+ and CD8+ T cell-related ceRNAs were identified as candidates for further studies.

Conclusion: ELK3 is a candidate immune-related gene in colon cancer. The chr22-38_28785274-29,006,793.1-miR-106a-5p-DDHD1 and chr22-38_28785274-29,006,793.1-miR-4319-GRHL1 axes may be related to CD4+ and CD8+ T cell infiltration in colon cancer.

Keywords: CD4+ T cells; CD8+ T cells; Colon cancer; Competing endogenous RNAs; Immunity.

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / immunology*
  • Colonic Neoplasms / mortality
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Prognosis
  • Protein Interaction Maps
  • Proto-Oncogene Proteins c-ets / genetics
  • Proto-Oncogene Proteins c-ets / physiology

Substances

  • Elk3 protein, human
  • Proto-Oncogene Proteins c-ets