Investigating the Impact of Bisphenol A on Gastric Cancer Through Network Toxicology and Molecular Docking

Abstract

The extensive application of bisphenol A (BPA), an endocrine-disrupting substance in polymer-based products and consumer commodities, has sparked concerns over its carcinogenic potential. However, the molecular mechanisms underlying BPA-induced gastric carcinogenesis remain poorly understood. We used network toxicology and molecular docking analysis to uncover the pivotal targets and mechanisms underlying BPA-associated gastric carcinogenesis. Potential BPA-related targets and differentially expressed genes in gastric cancer (GC) were collected from publicly available databases to identify hub genes. A prognostic risk assessment model utilizing hub genes, with molecular docking simulations, was performed to confirm the binding interactions between BPA and target proteins. A total of 27 potential targets associated with both BPA exposure and GC were identified. The protein-protein interaction network analysis revealed 19 hub genes, with core targets including MMP9, ADRB2, PTGS1, SLC6A4, ERBB2, MAPT, AR, SLC6A3, CNR1, PDE5A, DRD2, KCNH2, MC4R, CALCR, CHRM1, ADRB3, CXCR2, MMP1, and SHBG. Enrichment analysis demonstrated these hub genes were significantly involved in neuroactive ligand-receptor interaction, calcium signaling pathway, cGMP-PKG signaling pathway, and chemical carcinogenesis-receptor activation pathways. Prognostic analysis identified six hub genes (CALCR, ADRB3, CNR1, HRH2, KCNH2, and AR) significantly associated with patient survival. Molecular docking simulations demonstrated robust interaction affinities of BPA with the identified core target proteins. This study reveals that BPA may influence GC development and progression through multiple targets and signaling pathways, particularly involving G protein-coupled receptor signaling, hormone regulation, and neurological pathways.