TMEM132A is associated with metabolic reprogramming, macrophage-oriented immune remodeling, and breast cancer progression

Breast cancer progression reflects malignant cell programs coupled with immune remodeling. Biomarkers that connect tumor intrinsic states with microenvironmental interactions remain needed. We evaluated TMEM132A as a candidate marker in breast cancer. Bulk cohorts from The Cancer Genome Atlas, Genotype Tissue Expression, and Gene Expression Omnibus were analyzed to quantify TMEM132A expression, diagnostic discrimination, and associations with clinicopathologic features and survival. Single cell RNA sequencing and spatial transcriptomics localized TMEM132A across cell populations and tissue regions. Cell communication inference with correlation based validation and differential expression based enrichment, including GSEA and GSVA, were performed to characterize TMEM132A related biology. TMEM132A was consistently upregulated in tumors and separated tumor from normal tissue across datasets. High TMEM132A expression was associated with poorer outcomes and more advanced clinical categories. Single cell and spatial analyses localized TMEM132A mainly to malignant epithelial populations and tumor enriched regions, with reproducible links to macrophage related features. Cell communication analyses suggested that TMEM132A-positive malignant cells engage macrophage-associated signaling via the ANXA1–FPR3 and IL34–CSF1R axes; this inference was supported by correlation-based validation and is consistent with macrophage-oriented immune remodeling during breast cancer progression. TMEM132A-high tumors were enriched for cell cycle and DNA replication programs and showed higher activity in glycolysis, pentose phosphate pathway, oxidative phosphorylation, and pyrimidine metabolism. TMEM132A marks a malignant-associated state linked to adverse prognosis, proliferative and metabolic activation, and macrophage-oriented immune interactions, supporting its value for risk stratification and future mechanistic studies in breast cancer.