Advanced machine learning unveils CD8 + T cell genetic markers enhancing prognosis and immunotherapy efficacy in breast cancer.

BACKGROUND: Breast cancer (BC) is the most common cancer in women and poses a significant health burden, especially in China. Despite advances in diagnosis and treatment, patient variability and limited early detection contribute to poor outcomes. This study examines the role of CD8 + T cells in the tumor microenvironment to identify new biomarkers that improve prognosis and guide treatment strategies. METHODS: CD8 + T-cell marker genes were identified using single-cell RNA sequencing (scRNA-seq), and a CD8 + T cell-related gene prognostic signature (CTRGPS) was developed using 10 machine-learning algorithms. The model was validated across seven independent public datasets from the GEO database. Clinical features and previously published signatures were also analyzed for comparison. The clinical applications of CTRGPS in biological function, immune microenvironment, and drug selection were explored, and the role of hub genes in BC progression was further investigated. RESULTS: We identified 71 CD8 + T cell-related genes and developed the CTRGPS, which demonstrated significant prognostic value, with higher risk scores linked to poorer overall survival (OS). The model's accuracy and robustness were confirmed through Kaplan-Meier and ROC curve analyses across multiple datasets. CTRGPS outperformed existing prognostic signatures and served as an independent prognostic factor. The role of the hub gene TTK in promoting malignant proliferation and migration of BC cells was validated. CONCLUSION: The CTRGPS enhances early diagnosis and treatment precision in BC, improving clinical outcomes. TTK, a key gene in the signature, shows promise as a therapeutic target, supporting the CTRGPS's potential clinical utility.