Abstract
BACKGROUND: Long noncoding RNAs (lncRNAs) have been implicated in the development of hepatocellular carcinoma (HCC). Mounting evidence shows that lncRNAs can be used as prognostic biomarkers of HCC. Here, we developed a multi-lncRNA prognostic signature comprising ferroptosis-related lncRNAs in HCC. METHODS: Gene expression data and clinical information of HCC were obtained from the TCGA dataset. Differentially expressed genes of ferroptosis (DE-Ferrs) were screened. Correlation analysis was carried between lncRNAs and DE-Ferrs to identify ferroptosis-related lncRNAs. lncRNAs associated with prognosis and ferroptosis were identified using Univariate Cox analysis. Data from a TCGA dataset were randomly grouped into training and verification sets. The least absolute shrinkage and selection operator method analysis was carried out to identify lncRNAs with prognostic value. These lncRNAs were used to construct a prognostic signature using the training set. The signature was validated in the verification set. RESULTS: A total of 90 DE-Ferrs-related lncRNAs were identified which were significantly correlated with HCC prognosis. Seven lncRNAs were used to construct a 7-lncRNA signature. The area under the curves for 1-, 3-, and 5-year overall survival (OS) were 0.748, 0.681, and 0.659 in the training set, and 0.791, 0.731, and 0.815 in the validation set, respectively. The results demonstrated that a high-risk score was significantly associated with a high tumor grade, high infiltration of macrophages and fibroblasts in the tumor, and high expression of m6A methylation regulatory factors. A nomogram was constructed using the risk score and clinical features for predicting the prognosis of HCC. The nomogram showed high prediction accuracy. CONCLUSION: In conclusion, the established 7 ferroptosis-related lncRNAs signature can accurately predict HCC prognosis.