Network-based toxicological analysis of core targets and pathways of bisphenol A-driven hepatocellular carcinoma

Bisphenol A (BPA), an industrial compound widely used in plastics and food packaging, has been implicated in the development of various diseases. This study aims to elucidate the molecular toxicity mechanisms of BPA in hepatocellular carcinoma (HCC), providing a theoretical foundation for the prevention and treatment of HCC.

By retrieving BPA and HCC-associated genes from multiple databases and identifying their intersections, we performed protein-protein interaction (PPI) analysis and visualization of the intersecting genes. Potential mechanisms were explored through Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Core genes were identified using the Degree algorithm. Their expression levels in HCC were validated using the TCGA database, and Kaplan-Meier survival curves were constructed to demonstrate the impact of high versus low expression of these core genes on HCC patient prognosis. ROC curves were employed to assess the diagnostic performance of these core genes for HCC. The relationship between key prognostic genes and HCC immune cell infiltration was analyzed. Finally, molecular docking was utilized to further investigate the interactions between key prognostic genes and BPA.

A total of 101 intersecting genes were identified in BPA and HCC by multi-database analysis.GO and KEGG functional enrichment analysis showed that these intersected genes could affect HCC progression through multiple pathways.Five prognostic core genes, SRC, PPARG, HSP90AA1, MAPK3 and ESR1, were differentially expressed in HCC and were associated with poor prognosis of HCC patients. The ROC curves showed that the five prognostic core genes had good diagnostic and predictive properties. Meanwhile, an immune infiltration analysis suggested that the five prognostic genes had an important regulatory role in the immune microenvironment of HCC. In addition, molecular docking analysis further confirmed the potential interaction between BPA and the five prognostic core genes.

The results suggest that SRC, PPARG, HSP90AA1, MAPK3 and ESR1 play crucial roles in the development of HCC promoted by BPA. This provides new theoretical insights into the molecular mechanisms by which BPA promotes disease progression in HCC and offers potential therapeutic targets for early diagnosis, prognostic assessment, and targeted therapy for HCC.