Ferroptosis-related gene EPAS1 suppresses breast cancer progression by inhibiting M2 macrophage polarization.

OBJECTIVE: To investigate the role of the ferroptosis-related gene EPAS1 in breast cancer progression and its impact on macrophage polarization. METHODS: Bioinformatics and machine learning approaches were employed to identify ferroptosis-related differentially expressed genes (DEGs) in breast cancer tissues. Functional enrichment analysis was subsequently performed to explore the biological roles of these DEGs. The expression of EPAS1 was further analyzed in relation to macrophage polarization, with a particular focus on M1 and M2 macrophage infiltration. In addition, ROC curve analysis was conducted to evaluate the prognostic value of EPAS1 expression in predicting patient survival. RESULTS: A total of ferroptosis-related DEGs were identified by integrating GEO and TCGA datasets, among which EPAS1 and ACO1 were selected as key genes using machine learning algorithms. Functional enrichment analysis indicated that these genes were mainly involved in hypoxia response and cancer-related pathways. Survival analysis showed that high EPAS1 expression was significantly associated with improved overall survival, whereas ACO1 exhibited no prognostic significance. ROC curve analysis demonstrated that EPAS1 had moderate prognostic value, with an AUC of 0.837. Risk score analysis further revealed that patients in the high-risk group had poorer survival outcomes and lower EPAS1 expression levels compared to the low-risk group. Moreover, immune infiltration analysis indicated that EPAS1 expression was positively correlated with M1 macrophage infiltration and negatively correlated with M2 macrophage infiltration. CONCLUSION: EPAS1 functions as a key ferroptosis-related gene that regulates macrophage polarization in breast cancer by promoting M1 macrophage infiltration while suppressing M2 polarization. Targeting EPAS1 may represent a promising therapeutic strategy to enhance anti-tumor immunity and improve clinical outcomes in breast cancer patients.