Network toxicology and multiomics reveal bisphenol A-mediated immune evasion in breast cancer

ObjectiveTo test whether exposure to bisphenol A is related to immune modulation and prognosis in breast cancer using an integrative framework.MethodsBisphenol A targets from toxicology resources were intersected with breast cancer genes. Protein-protein interaction networks were constructed, and hubs were prioritized by centrality. Survival was evaluated in The Cancer Genome Atlas breast cancer cohort using Cox and Kaplan-Meier analyses. The tumor microenvironment was profiled using ESTIMATE scores and CIBERSORT deconvolution. Consistency was examined in the independent METABRIC cohort. Docking was used to estimate bisphenol A-protein binding free energies.ResultsFiltering converged on four immunoregulatory genes-<i>CCL19</i>, <i>CD40LG</i>, <i>IGLL5</i>, and <i>KLRB1</i>-linked to T cell activation and cytokine signaling. Their expression correlated with the levels of CD8+ T cells, memory B cells, and macrophages. Higher expression predicted improved overall survival in The Cancer Genome Atlas and showed consistent trends in METABRIC. Docking yielded negative free energies compatible with interference in immune signaling.ConclusionsThis integrative analysis connected environmental toxicology to tumor immunity and nominated CCL19, CD40LG, IGLL5, and KLRB1 as candidate biomarkers for exposure-risk assessment. The findings are correlative and require mechanistic validation.