A prognostic signature based on the expression profile of the ferroptosis-related long non-coding RNAs in hepatocellular carcinoma

Adv Clin Exp Med. 2022 May 18. doi: 10.17219/acem/149566. Online ahead of print.

Abstract

Background: Ferroptosis is a special form of cell death with extensive biological associations with various cancers; however, the role of aberrantly expressed ferroptosis-related long non-coding RNAs (lncRNAs) in hepatocellular carcinoma (HCC) remains unclear.

Objectives: To explore the role and prognostic value of ferroptosis-related lncRNAs in HCC and to screen potential therapeutic targets.

Material and methods: The RNA-seq data for 424 HCC patients and clinical data for 377 HCC patients were obtained from The Cancer Genome Atlas (TCGA) and evaluated using the Pearson's test to identify differentially expressed lncRNAs. The univariate analysis, least absolute shrinkage and selection operator Cox regression analysis were performed to construct and validate a prognostic risk-score model. The prognostic capacity was evaluated using the Kaplan-Meier method, univariate and multivariate Cox regression, and receiver operating characteristic (ROC) curve analyses. The enrichment analysis was performed to explore the functions of ferroptosis-related lncRNAs from the perspective of tumor immunology.

Results: Seventeen differentially expressed lncRNAs were identified (AL139384.1, AL928654.1, MKLN1-AS, AC145207.8, LINC00205, ZFPM2-AS1, LINC00942, POLH-AS1, AC090772.3, AL603839.3, AC012073.1, AC099850.1, AC026401.3, AP001469.3, AL031985.3, SNHG10, SNHG21) to establish the risk-score model. Survival analyses demonstrated poorer survival in high-risk patients, and the risk score was shown to be a better independent prognostic factor than conventional clinical characteristics. Additionally, we found close correlations between the risk score and immune cell subpopulation functions, as well as between the expression of immune checkpoint and carcinogenic N6-methyladenosine (m6A)-related mRNAs.

Conclusions: The novel ferroptosis-related lncRNA signature may serve as an individualized prognostic prediction tool for patients with HCC.

Keywords: ferroptosis; genes; hepatocellular carcinoma; immune response; long non-coding RNA.