Establishment of a prediction model of ferroptosis-related genes for overall survival risk in hepatocellular carcinoma and bioinformatic analysis of the novel gene FLT3

Abstract

Abstract Objective: Hepatocellular carcinoma (HCC) is a malignant tumor caused by malignant transformation of cells in the liver. It is the most common type of chronic liver cancer in adults. Ferroptosis has been found to play a key role in many tumor suppressions, but its prognostic value and key factors in hepatocellular carcinoma need to be further explored. Methods: We downloaded the RNAseq data and corresponding clinical information of HCC patients from TCGA database and ICGC database. The differential expression analysis and survival analysis of ferroptosis-related genes in tumor and normal tissues were carried out by R software. Univariate and multivariable cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression algorithm were used to build a overall survival (OS) risk prediction model for HCC in TCGA cohort, which was verified in ICGC cohort. The “immunedeconv” and "GSVA" packages were used to explore the important roles of single genes in HCC. Results: We successfully built a prediction model of 12 ferroptosis-related genes for overall survival risk in HCC, and confirmed the validity of the prediction model in the ICGC cohort. In addition, FLT3 gene was significantly associated with multiple pathways such as HCC tumor inflammation, Apoptosis, inflammatory response, and PI3K-AKT-mTOR. Conclusions: Ferroptosis plays a key role in the prognosis and treatment of primary HCC, and the prediction model of 12 ferroptosis-related genes for OS risk in HCC has significant effects. The ferroptosis-related gene FLT3, as a key immune-related factor, may become a new prognostic biomarker and a potential target for the treatment of HCC.