Molecular mechanism of bisphenol A in promoting esophageal carcinoma based on network toxicology and molecular docking.

Bisphenol A (BPA) is a pervasive endocrine-disrupting chemical with estrogenic activity and has been implicated in the development of multiple malignancies. However, its molecular mechanisms in esophageal carcinoma (ESCA) remain unclear. This study aimed to elucidate the potential oncogenic pathways through which BPA contributes to ESCA progression. Network toxicology was applied to collect BPA-related targets and ESCA-associated genes from multiple public databases. Overlapping targets were identified for further protein-protein interaction (PPI) and enrichment analyses to investigate functional pathways. Molecular docking was performed to assess binding affinities between BPA and core targets. The Cancer Genome Atlas (TCGA) was used for expression and survival validation, while mutation profiles were examined via cBioPortal. A total of 100 BPA-related targets and nearly 50,000 ESCA-associated genes were retrieved, yielding 95 overlapping targets. PPI network analysis and enrichment results highlighted HSP90AA1 and HSP90AB1 as central hub genes associated with protein kinase regulation, telomerase activity, and immune-inflammatory signaling pathways. Molecular docking confirmed strong binding affinities between BPA and HSP90AA1/HSP90AB1 (-7.5 and -7.0 kcal/mol, respectively). TCGA analyses showed that both genes were significantly upregulated in ESCA tissues, and high expression correlated with poorer overall survival. Mutation profiling indicated that HSP90AB1 exhibited a higher alteration frequency (13%), predominantly driven by gene amplification. This integrative multi-omics analysis provides compelling evidence that BPA may facilitate ESCA progression through HSP90AA1/HSP90AB1-mediated oncogenic and immune-inflammatory pathways. These findings deepen understanding of environmental carcinogenesis and suggest potential molecular targets for ESCA prevention and treatment.