Identification of novel ferroptosis biomarkers predicts the prognosis of hepatocellular carcinoma

Background: Ferroptosis is a newly recognized type of programmed cell death. This work aimed to explore unreported ferroptosis-related genes that have not been found to predict the prognosis of HCC; Methods: Candidate genes involved in the prognosis of HCC were identified from CROEMINE and FerrDb. Kaplan-Meier survival and Cox regression analysis were applied to assess the association of single gene and gene combinations with overall survival time (OS) and disease-free survival time (DFS) in TCGA cohort. Additionally, the predictor was further validated in the ICGC cohort. Real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were performed in HCC samples. Results: A total of 719 genes were included. Of these identified genes, 21 and 15 genes can predict OS and DFS, respectively, which had not been reported before. Survival analysis showed elevated mRNA expression of GLMP , SLC38A6 , and WDR76 were associated with poor prognosis and three genes combination signature was an independent prognostic factor in HCC. RT-qPCR and Immunohistochemistry confirmed the results; Conclusions: We established a novel computational process based on big data text-mining and bioinformatics analysis to explore new biomarkers of HCC associated with ferroptosis. Furthermore, after experimentally verified our result, we suggest that the expression of GLMP , SLC38A6 , and WDR76 may be used as potential ferroptosis-related biomarkers to evaluate the prognosis of patients with HCC.