Abstract
OBJECTIVE: Aromatic amines (AAs) have been verified as a risk factor for bladder cancer (BCa). Most existing studies have focused on specific AAs types in BCa and assessed the impact of exposure to AAs on the prognosis of BCa patients; however, there is no comprehensive exploration of the mechanism of action. Therefore, this study explored the core hub genes (CHGs) involved in the interaction between major AAs and BCa through multi-database joint analysis to clarify the molecular mechanism of the AAS-induced occurrence and development of BCa and provide innovative insights in the diagnosis and treatment of AAS-induced BCa. METHODS: After the toxicity analysis of AAs, the toxicity regulatory network of AAs in BCa was constructed through network toxicology, and the targets that showed the causal relationship with BCa were screened by Mendelian randomization (MR) analysis. Comprehensive mechanism exploration, molecular docking and drug prediction analysis were conducted on CHGs defined by the protein-protein interaction (PPI) network. RESULTS: The seven CHGs for the five AAs with different degrees of carcinogenicity to exert toxicity to BCa regulated the occurrence and development of BCa via multiple signaling pathways. Molecular docking confirmed the potential of the activation of these pathways caused by AAs. The results of drug prediction analysis suggested that rapamycin had a potential therapeutic prospect for AAs-induced BCa. CONCLUSION: This study reveals the underlying molecular mechanism by which exposure to AAs leads to the occurrence and development of BCa, providing novel preventive and therapeutic insights for populations exposed to this exposure factor.