A Novel Ferroptosis-Related Gene Signature For Clinically Predicting Recurrence After Hepatectomy of Hepatocellular Carcinoma Patients

Background: The high HCC recurrence rate was the main reason for the poor prognosis after hepatectomy. In this present study, we identified a novel ferroptosis-related gene signature for clinically predicting HCC recurrence after hepatectomy.Methods: Ferroptosis-related genes were obtained from the FerrDb database. We identified the ferroptosis-related differentially expressed genes (FDEGs) between HCC tissues and normal tissues from the GSE14520 dataset. These FDEGs were used to perform a univariate and multivariate regression analysis to construct HCC recurrence models. An independent HCC cohort from TCGA database was used to validate the reliability of the multi-gene HCC recurrence model. The predictive nomogram and DCA was built to estimate the recurrence predicting capacity of the multi-gene signature. GO, KEGG and GSEA were used to further investigate the potential mechanism of these FDEGs.Results: A total of 39 FDEGs were identified. A seven-gene signature (MAPK9, SLC1A4, PCK2, ACSL3, STMN1, CDO1, and CXCL2) was constructed for HCC recurrence prediction. Patients in high-risk groups exhibited a significantly poor prognosis compared with low-risk patients in both the training set (GSE14520 cohort) and the validation set (TCGA cohort). Multivariate cox regression analysis demonstrated that the 7-gene signature were independent risk factors for RFS in HCC patients. The nomograms incorporating 7-gene signature and clinical prognostic risk factors were able to effectively predict RFS. KEGG analysis showed that FDEGs were mainly enriched in Ferroptosis, Hepatocellular carcinoma pathway, MAPK signaling pathway, and so on. GSEA analysis revealed that the high-risk group was enriched with multiple oncology characteristics and invasive-related pathways.Conclusion: Our study constructed a seven ferroptosis-related gene signature and established a prognostic nomogram for clinically predicting recurrence after hepatectomy and offered novel research directions for personalized treatment in HCC patients.