Comparison of hepatic gene expression profiles between cirrhotic and non-cirrhotic HCC

Hepatocellular carcinoma (HCC) ranks among the leading causes of cancer-related deaths globally. Metabolic Associated Steatotic Liver Disease (MASLD), the most prevalent liver condition, is closely linked to a spectrum of hepatic disorders, including Metabolic Associated Steatohepatitis (MASH), liver cirrhosis, and eventually HCC. While cirrhosis is a well-established precursor to HCC, approximately 20% of HCC cases arise without prior cirrhosis, and the molecular mechanisms driving this subset of non-cirrhotic HCC remain poorly understood. This study employs a comprehensive bioinformatics approach to investigate the distinct molecular drivers of non-cirrhotic HCC compared to cirrhotic HCC. This study analyzed mRNA expression datasets to identify differentially expressed genes (DEGs) in MASLD/MASH versus normal tissue and cirrhotic and non-cirrhotic HCC versus normal tissue. GO analysis revealed that the DEGs were involved in pathways regulating lipid metabolism, cell proliferation, adhesion, migration, and immune responses, highlighting their diverse roles in tumorigenesis. Core genes involved in cell cycle regulation were identified and their expression patterns were systematically compared across MASLD/MASH, cirrhotic HCC, and non-cirrhotic HCC groups. Key genes such as CCNB1, E2F2, CDC25A, CCNE1, CDK1, CDKN2A, and CDKN2B showed significant upregulation in non-cirrhotic HCC compared to cirrhotic HCC, suggesting roles in driving tumorigenesis independent of cirrhosis. This comprehensive bioinformatics analysis identified core genes that mediate the molecular mechanisms underlying MASLD and MASH and their potential roles in non-cirrhotic HCC development. These findings provide a deeper understanding of the molecular basis of non-cirrhotic HCC and highlight promising biomarkers and therapeutic targets for diagnosing and managing this subset of HCC.