A novel cuproptosis-associated immune risk model for prediction of prognosis and response to immunotherapy in triple-negative breast cancer

Cuproptosis is closely associated with tumor progression and plays a role in tumor immunity. However, there is a lack of sufficient research on establishing a cuproptosis and immune-related risk model for predicting the prognosis and drug sensitivity of triple-negative breast cancer (TNBC). In this study, we collected clinical and gene expression data of TNBC patients from the TCGA and GEO databases. Based on cuproptosis-related genes, we identified two distinct cuproptosis patterns associated with immune response through consensus clustering and enrichment analyses. Thus, we constructed a prognostic cuproptosis-associated immune signature (CIS) in the TCGA-TNBC cohort and validated its predictive capacity in the GSE81540 and GSE58812 cohorts. TNBC patients with a high CIS exhibited significantly worse outcomes and higher rates of immune cell infiltration. Conversely, patients in the low-CIS group exhibited an immunosuppressive phenotype and potentially reduced sensitivity to immunotherapy. Furthermore, we predicted potential therapeutic agents for the low-CIS group and validated the levels of representative signature genes in cell lines and clinical samples. In all, We developed a novel risk model with cuproptosis and immune-related genes to predict OS and characterized immune microenvironment, and drug sensitivity, which might facilitate individual treatment of TNBC patients.