Comprehensive Analysis of Ferroptosis-related Genes in LiverCancer: Implications for Prognosis and Therapy

Introduction: This study aimed to investigate the role and prognostic significance of ferroptosis-related genes in hepatocellular carcinoma (HCC), with the goal of identifying potential biomarkers and therapeutic targets to improve early diagnosis and develop personalized treatment strategies for HCC. Methods: Various bioinformatics techniques were employed, including differential expression analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, consensus clustering, and Cox regression analysis Results: A total of 886 differentially expressed genes (DEGs) were identified, 35 of which were associated with ferroptosis. Immune cell infiltration analysis revealed significant alterations in the immune microenvironment, particularly involving regulatory T cells (Tregs), Th17 cells, and mast cells. The ferroptosis gene interaction network identified key genes, including EZH2 and NDRG1, with high connectivity, suggesting their critical roles in HCC. The Cox regression model demonstrated genes, such as EZH2, KIF20A, NDRG1, PPARG, KIF20A and MAPKAPK2, to be associated with poorer prognosis (P < 0.001), with an area under the curve (AUC) of 0.78 for risk prediction. Consensus clustering divided patients into two subgroups with significant survival differences (log-rank P < 0.001). Discussion: The findings underscored the crucial involvement of ferroptosis-related genes in the pathogenesis and progression of HCC. Key genes, such as EZH2 and NDRG1, appeared to influence both tumor biology and immune landscape, offering insights into mechanisms of tumor immune evasion and therapy resistance. While the study provided a robust computational framework, experimental validation is needed to confirm these observations and assess their translational potential. Conclusion: This study has highlighted the potential role of ferroptosis-related genes in hepatocellular carcinoma and identified EZH2, KIF20A, NDRG1, PPARG, KIF20A and MAPKAPK2 as key factors associated with poor prognosis.