Comprehensive transcriptomic analysis of hepatocellular Carcinoma: Uncovering shared and unique molecular signatures across diverse etiologies

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, often diagnosed at advanced stages where treatment options are limited. This study undertakes a comprehensive meta-analysis of gene expression profiles from 19 independent datasets sourced from the Gene Expression Omnibus (GEO), encompassing a diverse range of HCC etiologies, including HBV and HCV infections, cirrhosis, and normal liver comparisons. Our analysis identified 125 genes consistently altered across all datasets (e.g., CYP2C9, SLC22A1, RDH5) that represent a pan-etiology HCC signature, implicating retinol metabolism and solute transport as key pathways in HCC pathogenesis. Notably, 14 HBV-specific differentially expressed genes (DEGs) (e.g., ABCA8, GADD45B) and 221 HCV-specific DEGs (e.g., CDK1, CCNB1) were identified, highlighting etiology-specific molecular signatures. Protein-protein interaction (PPI) networks revealed central hubs (e.g., CDK1, CCNE1, TYMS) involved in cell cycle dysregulation and metabolic reprogramming (Warburg effect). These findings provide a robust molecular framework for HCC subtyping and prioritize novel biomarkers and therapeutic targets for further validation. This resource advances the potential for personalized HCC diagnostics and therapies.