ITM2A as a potential prognostic marker for triple-negative breast cancer

Different subtypes of breast cancer pose great challenges for precision therapy, especially triple-negative breast cancer (TNBC), because it lacks effective therapeutic targets and is highly resistant to chemotherapy. In this study, the transmembrane protein ITM2A was systematically identified as a novel prognostic biomarker and potential therapeutic target for TNBC. ITM2A was found to be significantly under expressed in TNBC tissues, as revealed by differential expression profiling. Furthermore, patients exhibiting low ITM2A expression demonstrated worse overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS). A combined multi-omics analysis revealed a significant association between low ITM2A expression and immunosuppressive microenvironmental features. It is noteworthy that the ITM2A high-expression group exhibited substantial clinical benefits in anti-PD-L1 treatment (AUC=0.982) and CAR-T treatment (AUC=0.827). Gene Ontology functional annotation and KEGG pathway enrichment analysis indicated that ITM2A may coordinate anti-tumor immune responses by regulating copper ion metabolic reprogramming and immune checkpoint networks. Pharmacogenomic analysis further confirmed that the expression level of ITM2A was negatively correlated with the sensitivity of etoposide. By establishing the 'immunometabolism-therapeutic response' regulatory axis of ITM2A, this study hopes to provide an innovative theoretical basis for the targeted treatment of TNBC and the precise stratification of immunotherapy.