Bioinformatics identification of shared signaling pathways and core targets linking Benzo[a]pyrene exposure to HCC progression

With the increasing prevalence of environmental pollutants, there is growing concern about the potential effects of these substances in major diseases such as liver cancer. Previous studies have suggested that various chemicals, such as benzo[a]pyrene(BaP), produced by burning carbon containing fuels, may negatively affect liver health, but the exact mechanisms remain unclear. This study aimed to explore the potential molecular mechanisms of BaP in the progression of liver cancer. Through an exhaustive study of databases such as ChEMBL, SwissTargetPrediction, STITCH and TCGA, we identified 169 potential targets that are closely related to BaP and liver cancer. Next, we conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses using the clusterProfiler package to study the biological functions and important pathways of potential targets induced by BaP, which showed that these targets were associated with mitochondrial function, cellular energy metabolism and REDOX reactions. The protein interaction (PPI) network was constructed using the STRING database and Cytoscape software to identify the core targets UBA52, NDUFS8, CYP1A2, NDUFS1 and CYP3A4. The interaction between BaP and these core proteins was further analyzed via molecular docking using the CB-Dock2 database, demonstrating high binding stability, which suggests their critical role in BaP-induced hepatocellular carcinoma (HCC) toxicity. Subsequently, we found significant differences in the expression of five core genes (UBA52, NDUFS8, CYP1A2, NDUFS1, CYP3A4) in HCC, and significant correlation between UBA52, NDUFS8 and CYP3A4 and survival of HCC patients. Single-cell sequencing analysis showed that the expression of UBA52 gene was particularly pronounced in the three immune cells.