Integrated single-cell and bulk RNA-seq analysis reveals a novel T-cell signature for prognosis and treatment response in colorectal cancer

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 (WGCNA), Lasso regression, and StepCox analysis, we developed a prognostic risk model, TRGS, 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 Immune Prognostic Score (IPS) and lower Tumor Immune Dysfunction and Exclusion (TIDE) scores in the low-risk group, indicating potential responsiveness to immune checkpoint inhibitor (ICI) therapy. Additionally, patients in the low-risk group demonstrated heightened sensitivity to 5-Fu-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.