Research Paper Volume 14, Issue 9 pp 4069—4084

Ferroptosis-related long non-coding RNA signature predicts the prognosis of hepatocellular carcinoma

Xin Yang1, *, , Minhui Mei1, *, , Jingze Yang1, , Jinlu Guo1, , Fan Du1, , Shi Liu1, ,

  • 1 Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
* Equal contribution

Received: August 23, 2021       Accepted: May 2, 2022       Published: May 12, 2022
How to Cite

Copyright: © 2022 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Background: Hepatocellular Carcinoma (HCC) is a highly heterogeneous malignant tumor, and its prognostic prediction is extremely challenging. Ferroptosis is a cell mechanism dependent on iron, which is very significant for HCC development. Long non-coding RNA (lncRNA) is also linked to HCC progression. This work aimed to establish a prognosis risk model for HCC and to discover a possible biomarker and therapeutic target.

Methods: The Cancer Genome Atlas (TCGA) database was used to obtain RNA-seq transcriptome data and clinic information of HCC patients. Firstly, univariate Cox was utilized to identify 66 prognostic ferroptosis-related lncRNAs. Then, the identified lncRNAs were further included in the multivariate Cox analysis to construct the prognostic model. Eventually, we performed quantitative polymerase chain reaction (q-PCR) to validate the risk model.

Results: We established a prognostic seventeen-ferroptosis-related lncRNA signature model. The signature could categorize patients into two risk subgroups, with the low-risk subgroup associated with a better prognosis. Additionally, the area under the curve (AUC) of the lncRNAs signature was 0.801, indicating their reliability in forecasting HCC prognosis. Risk score was an independent prognostic factor by regression analyses. Gene set enrichment analysis (GSEA) analyses demonstrated a remarkable enrichment of cancer-related and immune-related pathways in the high-risk group. Besides, the immune status was decreased in the high-risk group. Eventually, three prognostic lncRNAs were validated in human HCCLM3 cell lines.

Conclusions: The risk model based on seventeen-ferroptosis-related lncRNA has significant prognostic value for HCC and may be therapeutic targets associated with ferroptosis in clinical ways.


HCC: Hepatocellular Carcinoma; lncRNAs: long non-coding RNAs; TCGA: The Cancer Genome Atlas; AUC: The area under the curve; ROC: receiver operating characteristic; q-PCR: quantitative polymerase chain reaction; GSEA: Gene set enrichment analysis; FDR: false discovery rate; DEGs: differentially expressed genes; GO: Gene ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; DCA: decision curve analysis; OS: overall survival; PCA: principal component analysis; ssGSEA: single sample gene set enrichment analysis; ICIs: immune checkpoint inhibitors.