Unraveling the Molecular Links between Benzopyrene Exposure, NASH, and HCC: An Integrated Bioinformatics and Experimental Study

Abstract

Abstract Benzopyrene (B[a]P) is a widely recognized carcinogen that, upon chronic exposure, can induce chronic inflammation and fibrosis in liver tissue, ultimately resulting in liver disease. Nonalcoholic steatohepatitis (NASH) is a chronic liver condition characterized by fat accumulation, inflammation, and fibrosis, often resulting in hepatocellular carcinoma (HCC). This study aimed to investigate the intricate connections between B[a]P exposure, NASH, and HCC. Through comprehensive bioinformatics analysis, we identified differentially expressed genes (DEGs) associated with B[a]P exposure, NASH, and liver cancer using publicly available gene expression profiles. Subsequent network analysis revealed hub genes and protein-protein interactions, highlighting cellular metabolic dysfunction and disruption of DNA damage repair in the B[a]P-NASH-HCC process. Particularly, HSPA1A and PPARGC1A emerged as significant genes in this pathway. To validate their involvement, we performed qPCR in NASH mouse liver tissues and immunohistochemistry labeling in mouse and human HCC liver sections. Our findings providing crucial insights into the potential regulatory mechanisms underlying benzopyrene-induced hepatotoxicity. These results shed light on the pathogenesis of B[a]P-associated NASH and HCC and suggest that HSPA1A and PPARGC1A hold promise as therapeutic targets. Enhancing our understanding of their regulatory roles may facilitate the development of targeted therapies, leading to improved patient outcomes.