Unveiling the Clinical Significance of RACGAP1 in a Senescence Gene and Immune Score Based Prognostic Model for Breast Cancer

Background: Intrinsic tumor cell factors and the tumor microenvironment (TME) are critical for breast cancer prognosis. This study established a novel prognostic model integrating senescence-associated gene expression and immune scores, and explored the clinical significance of core gene RACGAP1 and its correlation with TME. Methods: Differentially expressed genes were screened from TCGA-BRCA cohort (n = 1222, FDR < 0.05) and combined with ESTIMATE immune scores. Eighty-one senescence-associated genes were obtained via intersection with CellAge database. Top 20 hub genes were identified by PPI network, and four prognostic genes via univariate Cox analysis; multivariate Cox and LASSO regression pinpointed RACGAP1 as the core target. Data were divided into training (n = 420) and internal validation (n = 419) sets, with GSE7390 (n = 198) for external validation. Results: GO/KEGG analyses revealed RACGAP1 participated in immune response and cell cycle regulation. Multivariate Cox confirmed high RACGAP1 expression was an independent poor prognostic risk factor (HR = 1.81, 95%CI=1.10-2.98, p = 0.019). The RACGAP1-centered model showed strong predictive ability, with 3/5-year AUC 0.80/0.75, C-index 0.772 (internal) and 0.71 (external). The integrated nomogram had excellent calibration (Brier score < 0.2). Conclusion: RACGAP1 is a novel prognostic biomarker for breast cancer, and the established model has reliable predictive efficacy, providing a reference for prognosis evaluation and targeted therapy.