Abstract
Breast invasive carcinoma (BRCA) is the most commonly diagnosed cancer in women and exhibits the highest mortality rate among female cancers. Furthermore, the tumor microenvironment (TME) plays a crucial role in the progression of BRCA. Copper ions are essential metal elements in vivo, and cuproptosis, a recently identified mode of cell death, significantly influences tumor progression, metastasis, and angiogenesis. Utilizing 10 cuproptosis-related genes (CRGs), we developed a novel cuproptosis-tumor immunological phenotype-related gene score (CTIPRGs) comprising 14 genes through Univariate Cox (UniCOX) regression and the least absolute shrinkage and selection operator (LASSO) algorithm to predict prognosis and response to immunotherapy in BRCA. Univariate and multivariate analyses indicated that CTIPRGs serve as an independent prognostic predictor. Subsequently, we constructed nomograms to provide quantitative tools for clinical practice. Kaplan-Meier (KM) plot analysis demonstrated that CTIPRGs could significantly distinguish overall survival (OS) in BRCA patients, with low-CTIPRGs groups exhibiting better prognosis. High and low-CTIPRGs groups exhibited distinct biological behaviors, mutational characteristics, and immune cell infiltration patterns. Notably, low-CTIPRGs groups were classified as an immune-inflamed phenotype with abundant immune cells, whereas high-CTIPRGs groups were identified as immune-desert phenotypes characterized by extensive stromal cell infiltration. Additionally, notable differences in tumor immunogenicity, tumor immune dysfunction and exclusion (TIDE), and tumor mutation burden (TMB) were observed between high and low-CTIPRGs groups, indicating that low-CTIPRGs groups exhibited higher sensitivity to immunotherapy. In conclusion, the identified CTIPRGs can facilitate the prediction of prognosis and treatment efficacy in BRCA patients.