Multi-omics investigation of Bisphenol A in gastrointestinal carcinogenesis: a network toxicology and molecular docking approach

作者：Jiayun Guan, Ke Yang, Tianyang Chen, Z Li, Ya Gao, Yue Huang, Rui Zhou, Zhenhua Huang, Yangfeng Du, Tao Li, Baoxiong Zhuang, Xiaoxiang Rong · 发表于：Environment International · 年份：2025 · DOI：10.1016/j.envint.2025.109785 · 被引用次数：6 · 研究领域：Effects and risks of endocrine disrupting chemicals、Cancer Cells and Metastasis、Molecular Biology Techniques and Applications

Our study aims to systematically investigate the potential carcinogenic mechanisms of bisphenol A (BPA) in three gastrointestinal tumors: intrahepatic cholangiocarcinoma (ICC), colorectal cancer (CRC), and esophageal cancer. By systematically integrating multi-omics databases, including transcriptomics and single-cell transcriptomics, we identified overlapping targets between BPA-associated molecules and tumor-related genes. Functional enrichment revealed that these targets converge on key oncogenic pathways, includingcellular metabolic reprogramming (particularly glycolysis), tumor microenvironment remodeling via cancer-associated fibroblast (CAF) activation, and dysregulation of cell cycle progression. Molecular docking verified strong binding affinity between BPA and key targets. Survival analysis linked GAPDH and HSP90AA1 in ICC, CDKN1A, CEBPB, and EGR1 in CRC, and DCN and CXCL12 in esophageal cancer to poor survival rates, highlighting their potential as prognostic biomarkers. Our findings demonstrate that BPA promotes gastrointestinal carcinogenesisthrough disrupting energy metabolism, activating CAFs to remodel the tumor microenvironment, and enhancing cancer cell proliferation. This multi-level evidence advances the risk assessment of BPA and identifies potential targets for prevention and therapy of BPA-linked gastrointestinal cancers. Environmental Implication. In addition to well-documented role in promoting endocrine-related diseases, the mechanisms by which hazar...