Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks effective therapeutic options. Hypoxia and immune escape are critical factors that contribute to the progression of and resistance to therapy in patients with TNBC. Nevertheless, few studies have comprehensively analyzed hypoxia and immune escape in patients with TNBC. This study aimed to examine the expression of hypoxia- and immune escape-related genes in TNBC and their influence on prognosis. TNBC datasets were downloaded and processed from The Cancer Genome Atlas and Gene Expression Omnibus. Differential expression analysis identified 4949 differentially expressed genes, between TNBC and normal tissues. The intersection yielded 116 hypoxia- and immune escape-related differentially expressed genes (H&IERDEGs), including KIF4A, BIRC5, and BUB1. Enrichment analyses indicated that H&IERDEGs were significantly enriched in biological processes, including cell chemotaxis, leukocyte migration, and cytokine-cytokine receptor interaction. Subsequently, weighted gene co-expression network analysis identified 43 module genes that were found to define two TNBC subtypes. We constructed a prognostic risk model consisting of eight signature genes, which demonstrated a high predictive performance to predict the overall survival (OS) of patients with TNBC with an area under the curve (AUC) exceeding 0.9 at 1 year survival. This indicates that the model effectively differentiates between outcomes, reflecting its robust performance. This study investigated the roles and potential mechanisms of hypoxia- and immune escape-related genes in TNBC and constructed a prognostic risk model with a high predictive performance. These findings offer novel molecular markers and potential therapeutic targets for TNBC.
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