A Novel Ferroptosis-Related Signature for Prediction of Prognosis, Immune Profiles and Drug Sensitivity in Hepatocellular Carcinoma Patients

Abstract

Hepatocellular carcinoma (HCC) is a malignant disease with an increasing incidence and a high mortality rate. Ferroptosis, a novel type of cell death, has been reported to be closely associated with the progression of HCC. The aim of our study was to construct a novel ferroptosis-related signature (nFRGs) for prediction of prognosis, immune features and drug sensitivity of HCC patients. Data were obtained from the TCGA, ICGC, GSE104580, CCLE and IMvigor210 datasets, and the least absolute shrinkage and selection operator (LASSO) was used to construct nFRGs. In addition, the analyses involved in prognoses, molecular function, stemness indices, somatic mutation, responses to immunologic therapy, efficacy of transcatheter arterial chemoembolization (TACE) therapy and drug sensitivity were performed using diverse packages of R 4.1.3 between the low- and high-risk groups. The nFRGs included seven ferroptosis-related genes. Our results showed that nFRGs was an independent risk factor for prognoses of HCC patients, and HCC patients in the high-risk group presented with worse prognosis. Compared with the results of other studies, nFRGs was superior to other promising signatures in predicting prognoses of patients with HCC. In addition, most of the enriched pathways of differentially expressed genes (DEGs) between these subgroups were related to immune features. The molecular functions, genetic mutation and mRNAsi were varied between the high- and low-risk groups. Moreover, we observed significant immunosuppression state in the high-risk group. Patients in the high-risk group might benefit from immunotherapy, whereas patients in the low-risk group may be susceptible to TACE therapy. Finally, five sensitive drugs and four sensitive drugs were screened for patients in the high- and low-risk groups, respectively. nFRGs may served as a novel biomarker of prognosis and aid in personalized therapeutic strategies for patients with HCC.