Network toxicology and multidimensional bioinformatics analysis reveal the shared mechanism of action of bisphenol A and phthalates in glioblastoma

BACKGROUND: Bisphenol A (BPA) and phthalates, as prevalent endocrine-disrupting chemicals (EDCs), have been involved in the development of different cancers; however, their shared molecular mechanisms in glioblastoma (GBM) remain largely unexplored. METHODS: This study systematically explored the shared targets and signaling pathways of BPA and phthalates in glioblastoma (GBM) by integrating multiple advanced approaches, including network toxicology, single-cell RNA sequencing (scRNA-seq), TCGA analysis, and bibliometric analysis. RESULTS: A total of 130 shared targets between EDCs and GBM were identified. Functional and PPI analyses highlighted ATM, CDK1, and CDKN2A as hub genes. ATM and CDK1 showed strong diagnostic value (AUC = 0.791, 0.997). ssGSEA and GSVA revealed their roles in immune modulation and tumor signaling. Single-cell and docking analyses confirmed cell-type-specific expression and strong EDC binding. Finally, bibliometric analysis delineated the emerging hotspots and evolving trends in CDK1 and GBM research. CONCLUSION: This study elucidates the potential pathways through which BPA and phthalates contribute to GBM development via shared molecular mechanisms, offering a theoretical foundation for the identification of relevant diagnostic biomarkers and therapeutic targets.