Integrated single-cell and bulk RNA-seq analysis identifies a prognostic T-cell signature in colorectal cancer

Sci Rep. 2024 Aug 30;14(1):20177. doi: 10.1038/s41598-024-70422-6.

Abstract

Colorectal cancer (CRC) is a major contributor to global morbidity and mortality, necessitating more effective therapeutic approaches. T cells, prominent in the tumor microenvironment, exert a crucial role in modulating immunotherapeutic responses and clinical outcomes in CRC. This study introduces a pioneering method for characterizing the CRC immune microenvironment using single-cell sequencing data. Unlike previous approaches, which focused on individual T-cell signature genes, we utilized overall infiltration levels of colorectal cancer signature T-cells. Through weighted gene co-expression network analysis, Lasso regression, and StepCox analysis, we developed a prognostic risk model, TRGS (T-cell related genes signatures), based on six T cell-related genes. Multivariate Cox analysis identified TRGS as an independent prognostic factor for CRC, showcasing its superior predictive efficacy compared to existing immune-related prognostic models. Immunoreactivity analysis revealed higher Immunophenoscore and lower Tumor Immune Dysfunction and Exclusion scores in the low-risk group, indicating potential responsiveness to immune checkpoint inhibitor therapy. Additionally, patients in the low-risk group demonstrated heightened sensitivity to 5-fluorouracil-based chemotherapy regimens. In summary, TRGS emerges as a standalone prognostic biomarker for CRC, offering insights to optimize patient responses to immunotherapy and chemotherapy, thereby laying the groundwork for personalized tumor management strategies.

Keywords: Chemotherapy; Colorectal cancer; Immune checkpoint inhibitors; Prognostic risk model; T cell.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / immunology
  • Colorectal Neoplasms* / mortality
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Prognosis
  • RNA-Seq*
  • Single-Cell Analysis* / methods
  • T-Lymphocytes* / immunology
  • T-Lymphocytes* / metabolism
  • Transcriptome
  • Tumor Microenvironment* / genetics
  • Tumor Microenvironment* / immunology

Substances

  • Biomarkers, Tumor