Abstract
OBJECTIVES: Breast cancer patients with diabetes are often associated with poor prognosis. This study aims to investigate the role of metformin in ferroptosis and cuproptosis in diabetic breast cancer patients and explore its potential impact on clinical outcomes. METHODS: We retrospectively analyzed tissue samples from 16 breast cancer patients, including 5 non-diabetic and 11 diabetic patients (6 treated with metformin). Immunohistochemistry (IHC) staining was performed for cuproptosis (FDX1, DLAT), ferroptosis (ACSL4, GPX4), and glycolysis markers (LDHA, PKM2). Statistical analysis used quantitative results from immunohistochemistry. RESULTS: Patients treated with metformin showed significantly higher expression of FDX1 and ACSL4, along with a significant decrease in GPX4 compared to other groups. Kaplan-Meier survival analysis revealed that high FDX1 expression was associated with longer survival in breast cancer patients. Correlation analysis showed a positive association between ACSL4 and FDX1 (R = 0.51, P = 0.045), suggesting a relationship between these markers. CONCLUSIONS: Metformin may simultaneously enhance both cuproptosis and ferroptosis in breast cancer. FDX1 expression could serve as a prognostic marker for survival, especially in diabetic patients, providing insights into targeting metabolic and cell death pathways in breast cancer therapy.