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A Prognostic Model for Hepatocellular Carcinoma Based on Known Ferroptosis-Related Long Non-coding RNA

Congyue Zhang1,2, Chaoqun Zhang1,2, Huifang Zhou2, Zhankai Hu1, Dianxing Sun2*

Background: Hepatocellular Carcinoma (HCC) is a prevalent malignancy worldwide, and ferroptosis is an iron-dependent cell death process. In addition, the aberrant expression of long noncoding RNAs (lncRNAs) that contribute to the development and progression of HCC has garnered increased interest.

Materials and methods: We collected lncRNA expression profiles associated with ferroptosis and clinicopathological information from The Cancer Genome Atlas (TCGA) and FerrDb databases. The relationship between ferroptosis-related lncRNAs (FRlncRNAs) and HCC patients survival is determined by co-expression analysis of Overall Survival (OS). Using cox regression analysis and the LASSO algorithm, a prognostic lncRNA model of 22 differentially expressed lncRNAs was developed.

Results: High-risk lncRNA profile was associated with a poor prognosis in HCC, as determined by a Kaplan-Meier analysis. In predicting the prognosis of HCC, our risk assessment model outperformed conventional clinical data. GSEA uncovered immune and tumor-related pathways in high-risk and low-risk individuals. In addition, TCGA revealed that T cell functions, such as B cells, cytolytic macrophages, MHC-class-I, mast cells, neutrophils, NK cells, helper T cells, Type-I-IFN, and Type-II-IFN, differed significantly between high-risk groups and low-risk groups. Immune checkpoints were also differentially expressed between the risk groups, including TNFSF18, IDO2, CD276, NRP1, and TNFSF4.

Conclusion: Based on lncRNAs associated with ferroptosis, our findings provide a robust prog-nostic and immune response prediction model for HCC patients.