Identification of Ferroptosis-related Genes Associated with the Prognosis of Hepatocellular Carcinoma

Ferroptosis has been increasingly implicated in the progression of various tumors, including hepatocellular carcinoma (HCC). This study aimed to identify ferroptosis-related genes with prognostic significance in HCC. Differential expressed genes (DEGs) and long non-coding RNAs (DElncRNAs) were identified from TCGA LIHC RNA-seq data. A competitive endogenous RNA (ceRNA) network was established based on ferroptosis-related lncRNA-mRNA pairs. Prognostic genes were identified through survival analysis, and selected DEGs were further validated via quantitative PCR. Co-expression analysis identified 218 lncRNA-mRNA pairs, including 216 DEGs and 11 DElncRNAs. Among these, 11 upregulated ferroptosis-related genes were identified as predicted targets of the lncRNA DDX11-AS1. MiR-195 and miR-424 both regulated CDC25A and HELLS. Elevated expression of DDX11-AS1, CDC25A, EZH2, FANCD2, and HELLS was associated with poorer survival. In vitro cellular experiments showed that the knockdown of DDX11-AS1, CDC25A, and HELLS inhibited cell proliferation and invasion by promoting ferroptosis in Huh7 cells. The 11 ferroptosis-related genes and DDX11-AS1 may serve as valuable prognostic biomarkers and potential immunotherapeutic targets in HCC.