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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.<\/jats:p>","DOI":"10.1007\/s12013-026-02096-y","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T09:55:06Z","timestamp":1782381306000},"page":"3951-3965","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Ferroptosis-related Genes Associated with the Prognosis of Hepatocellular Carcinoma"],"prefix":"10.1007","volume":"84","author":[{"given":"Kai","family":"Yan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haodong","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahua","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"2096_CR1","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.ejca.2017.10.010","volume":"87","author":"GS Roth","year":"2017","unstructured":"Roth, G. 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Informed consents were obtained from all patients before surgeries.","order":1,"name":"Ethics","label":"Ethical Approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","label":"Conflict of Interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}