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.

Multi-omics Analysis of Prognostic Significance and Immune Infiltration of FASTK Family Members in Kidney Renal Clear Cell Carcinoma

“…Using the patient data from TCGA, the clinical meaning module of the Xiantao platform ( https://www.xiantao.love/ ) 22 was adopted to evaluate prognostic metrics, notably, overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). Both the Cox regression and Kaplan-Meier were applied to perform these analyses.…”

Deciphering hepatocellular carcinoma pathogenesis and therapeutics: a study on anoikis, ceRNA regulatory network and traditional Chinese medicine

“…Using LASSO Cox regression analysis, we developed a prognostic model that incorporates five ARGs (BIRC5, E2F1, SFN, SPP1, and UBE2C), which have been found to be significant in the context of HCC. Previous studies have highlighted the prognostic importance of specific gene sets in HCC, including genes associated with ferroptosis (Zhang Y. et al, 2022;Zhao et al, 2022), glycolytic-related genes (Zou et al, 2022), and ARGs (Guizhen et al, 2022;Chen et al, 2023) are closely The interaction between ten TCM active components and BIRC5 protein was simulated by molecular docking (A-J) and the expression of the core genes in the regulatory network of three ceRNAs regulatory network in LX2, HepG2 and Huh7 cells based on qRT-PCR assay (K-O). Frontiers in Pharmacology frontiersin.org associated with HCC prognosis.…”

Ferroptosis and cuproptosis prognostic signature for prediction of prognosis, immunotherapy and drug sensitivity in hepatocellular carcinoma: development and validation based on TCGA and ICGC databases

“…We compared our own model to 12 other published HCC prognostic models to better show its predictive power (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31). Multivariate analysis was used to calculate the risk value and prognostic evaluation for each dataset, leveling the playing field amongst the four models.…”