Role of SERPINA1 in the tumor immune microenvironment of breast cancer and construction of a prognostic model

Breast cancer is a common malignancy where the immune system plays a key role in disease progression and treatment response. SERPINA1 is an immune-related gene, but its function in breast cancer remains unclear. This study explored the expression, immune role, and prognostic value of SERPINA1 in breast cancer. We analyzed data from TCGA and other public databases to evaluate SERPINA1 expression and performed Western blot and qPCR experiments for validation. Various bioinformatics tools were used to assess immune-related functions, identify differentially expressed genes, conduct pathway enrichment analyses, and construct a prognostic risk model. External datasets were used for validation, and immune activity and drug sensitivity were compared between different risk groups. SERPINA1 was significantly overexpressed in breast cancer tissues compared to normal tissues, and high expression was associated with better overall survival. High SERPINA1 expression correlated with enhanced activation of immune-related pathways, such as T and B-cell signaling. Patients with high SERPINA1 levels showed higher immune and stromal scores, increased infiltration of CD8⁺ T cells, macrophages, and dendritic cells, and elevated expression of immune checkpoint molecules. A prognostic model based on SERPINA1-associated immune genes effectively stratified patient survival risk and was validated in multiple external datasets. Patients in the low-risk group had stronger immune activity and were more sensitive to various chemotherapy and targeted drugs, suggesting the model’s potential in guiding personalized treatment. SERPINA1 is closely linked to favorable prognosis and an active immune microenvironment in breast cancer. The SERPINA1-based prognostic model may be useful for survival prediction and personalized immunotherapy strategies.