The Detection and Verification of Two Heterogeneous Subgroups and a Risk Model Based on Ferroptosis-Related Genes in Hepatocellular Carcinoma

Abstract

#Background. Because of the heterogeneity of hepatocellular carcinoma (HCC) and the complex nature of the tumor microenvironment (TME), the long-term efficacy of therapy continues to be a clinical challenge. It is necessary to classify and refine the appropriate treatment intervention decision-making in this kind of tumor. Methods. We used "ConsensusClusterPlus"to establish a stable molecular classification based on the ferroptosis-related genes (FRGs) expression obtained from FerrDb. The clinical features, immune infiltration, DNA damage, and genomic changes of different subclasses were evaluated. The least absolute shrinkage and selection operator regression (LASSO) method and univariate Cox regression were utilized to construct the ferroptosis-related prognosis risk score (FPRS) model, and the association between the FPRS model and HCC molecular characteristics, immune features, and immunotherapy was studied. Results. We identified two ferroptosis subclasses, C1 with poor prognosis and a higher proportion of patients in the middle and late stages infected with HBV and HCV, having higher DNA damage including aneuploidy, HRD, fraction altered, and the number of segments, and higher probability of gene mutation and copy number mutation. FPRS model was constructed on the basis of differentially expressed genes (DEGs) between C1 and C2, which showed a higher area under the curve (AUC) in predicting overall survival rate in the training set and independent verification cohort and could reflect the clinical characteristics and response to immunotherapy of different patients, being an independent prognostic factor of HCC. Conclusion. Here, we revealed two novel molecular subgroups based on FRGs and develop an FPRS model consisting of six genes that can help predict prognosis and select patients suitable for immunotherapy.