Machine learning-based model for CD4+ conventional T cell genes to predict survival and immune responses in colorectal cancer

• Published in: Scientific reports Vol. 14; no. 1; pp. 24426 - 15
• Main Authors: Wang, Zijing, Sun, Zhanyuan, Lv, Hengyi, Wu, Wenjun, Li, Hai, Jiang, Tao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18-10-2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/67; 692/53; Biomarkers; Biomarkers, Tumor - genetics; CD4 antigen; CD4+ conventional T cells-related genes; CD4-Positive T-Lymphocytes - immunology; Chemotherapy; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - immunology; Colorectal Neoplasms - mortality; Female; Humanities and Social Sciences; Humans; Immunotherapy; Kaplan-Meier Estimate; Learning algorithms; Lymphocytes T; Machine Learning; Male; Malignancy; Mortality; multidisciplinary; Patients; Prognosis; Regression analysis; Risk assessment; Science; Science (multidisciplinary); Single-cell; Survival; Survival analysis; Transcriptome; Transcriptomics; Tumor Microenvironment - genetics; Tumor Microenvironment - immunology; CD4; conventional T cells-related genes; Prognosis; Single-cell; Colorectal cancer; Machine learning; CD4+ conventional T cells-related genes
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-75270-y

Globally, CRC ranks as a principal cause of mortality, with projections indicating a substantial rise in both incidence and mortality by the year 2040. The immunological responses to cancer heavily rely on the function of CD4Tconv. Despite this critical role, prognostic studies on CRC-related CD4Tconv remain insufficient. In this investigation, transcriptomic and clinical data were sourced from TCGA and GEO. Initially, we pinpointed CD4TGs using single-cell datasets. Prognostic genes were then isolated through univariate Cox regression analysis. Building upon this, 101 machine learning algorithms were employed to devise a novel risk assessment framework, which underwent rigorous validation using Kaplan-Meier survival analysis, univariate and multivariate Cox regression, time-dependent ROC curves, nomograms, and calibration plots. Furthermore, GSEA facilitated the examination of these genes’ potential roles. The RS derived from this model was also analyzed for its implications in the TME, and its potential utility in immunotherapy and chemotherapy contexts. A novel prognostic model was developed, utilizing eight CD4TGs that are significantly linked to the outcomes of patients with CRC. This model’s RS showcased remarkable predictive reliability for the overall survival rates of CRC patients and strongly correlated with malignancy levels. RS serves as an autonomous prognostic indicator, capable of accurately forecasting patient prognoses. Based on the median value of RS, patients were categorized into subgroups of high and low risk. The subgroup with higher risk demonstrated increased immune infiltration and heightened activity of genes associated with immunity. This investigation’s establishment of a CD4TGs risk model introduces novel biomarkers for the clinical evaluation of CRC risks. These biomarkers may enhance therapeutic approaches and, in turn, elevate the clinical outcomes for patients with CRC by facilitating an integrated treatment strategy.