Integrated network toxicology and multi-omics analysis reveals Benzo(a)pyrene-driven molecular networks and...

Benzo(a)pyrene (BaP), an environmental carcinogen, contributes to colon cancer pathogenesis through incompletely elucidated mechanisms. This study integrated network toxicology and multi-omics analyses to decipher BaP-associated molecular signatures and clinical relevance in colon cancer. Using TCGA-COAD data, 113 differentially expressed BaP-related targets were identified via CTD and Super-PRED databases. PPI networks, functional enrichment, and Cox/Lasso regression revealed key pathways (xenobiotic metabolism, p53 signaling, cell cycle) and six prognostic genes (CLK2, CRYAB, RPS6KA1, DPP7, CDC25C, GAST). A BaP-related risk model stratified patients into distinct survival groups. A nomogram accurately predicted 1-, 3-, and 5-year overall survival. High-risk scores correlated with advanced tumor stage, metastasis, and immunosuppressive microenvironments. Molecular docking demonstrated strong BaP binding to CLK2 and CRYAB. External validation (GSE39582, TNMplot) confirmed tumor-specific gene expression patterns. These findings delineate BaP-driven networks connecting xenobiotic stress, immune dysregulation, and tumor progression. The risk model provides a prognostic biomarker for personalized management and therapeutic targeting in colon cancer.