Identification and Validation of Tumorigenesis Related Hub Genes in Hepatocellular Carcinoma via Integrated Bioinformatics Analysis.

[BACKGROUND] Hepatocellular carcinoma (HCC) is a heterogeneous liver cancer with poor prognosis and diverse etiologies, yet molecular mechanisms across different causes remain unclear.

[OBJECTIVE] To identify key gene expression patterns and pathways associated with HCC progression from diverse pathological backgrounds using integrated bioinformatics analysis.

[MATERIALS AND METHODS] Seven HCC-related GEO datasets totaling 1219 samples were analyzed. Differentially expressed genes (DEGs) were identified, followed by pathway enrichment, survival analysis, and immunohisto-chemistry validation.

[RESULTS] We identified DEGs such as CBS, ELF3, SPP2, and RPL8 correlated with patient survival. Enrichment analysis highlighted the PI3K-Akt signaling pathway as a central route in liver cirrhosis and tumor progression. A 47-gene set was proposed as a potential regulatory 'brake' during benign-to-malignant transformation. These findings were consistent with recent studies emphasizing PI3K-Akt and metabolic dysregulation in HCC pathogenesis.

[CONCLUSIONS] Our integrative analysis reveals critical genes and pathways involved in HCC development, providing potential prognostic biomarkers and therapeutic targets. The study underscores the importance of cirrhosis in HCC progression and highlights the PI3K-Akt pathway's pivotal role. Further functional validation and larger cohort studies are warranted.