Network toxicology and multiomics reveal bisphenol A-mediated immune evasion in breast cancer
Yu Fang1, Jia-Li Yan2, Wang Zhang1
1Department of Pharmacy, The Third People's Hospital of Hefei, Hefei Third Clinical College of Anhui Medical University, China.
Abstract:
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-CCL19, CD40LG, IGLL5, and KLRB1-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.
Insights
Exposure to bisphenol A may influence breast cancer by modulating immune cells. Four genes (CCL19, CD40LG, IGLL5, KLRB1) linked to immune response were identified as potential biomarkers for risk assessment.
Area of Science:
- Environmental toxicology
- Cancer immunology
- Molecular biology
Background:
- Bisphenol A (BPA) is an environmental toxicant with potential endocrine-disrupting properties.
- Breast cancer involves complex interactions between tumor cells and the immune microenvironment.
- Understanding the link between environmental exposures and cancer immunity is crucial for risk assessment.
Purpose of the Study:
- To investigate the relationship between bisphenol A exposure, immune modulation, and breast cancer prognosis.
- To identify potential immunoregulatory genes affected by BPA exposure in breast cancer.
Main Methods:
- Integrative analysis of BPA targets and breast cancer genes.
- Construction and analysis of protein-protein interaction networks.
- Survival analysis in The Cancer Genome Atlas (TCGA) and METABRIC cohorts.
- Tumor microenvironment profiling using ESTIMATE and CIBERSORT.
- Molecular docking to assess BPA-protein binding.
Main Results:
- Four immunoregulatory genes (CCL19, CD40LG, IGLL5, KLRB1) were identified, associated with T cell activation and cytokine signaling.
- Gene expression correlated with immune cell infiltration (CD8+ T cells, B cells, macrophages).
- Higher expression of these genes predicted improved overall survival in both TCGA and METABRIC cohorts.
- Molecular docking suggested BPA may interfere with immune signaling pathways.
Conclusions:
- This study links environmental toxicology (BPA) to breast cancer immunity and prognosis.
- CCL19, CD40LG, IGLL5, and KLRB1 are nominated as candidate biomarkers for BPA exposure-risk assessment.
- Findings are correlative and warrant further mechanistic validation.
