Comprehensive analysis of N6 -methyladenosine-related long non-coding RNAs for prognosis prediction in liver hepatocellular carcinoma.

Abstract

BackgroundLiver hepatocellular carcinoma (LIHC) is a lethal cancer. This study aimed to identify the N6‐methyladenosine (m6A)‐targeted long non‐coding RNA (lncRNA) related to LIHC prognosis and to develop an m6A‐targeted lncRNA model for prognosis prediction in LIHC.MethodsThe expression matrix of mRNA and lncRNA was obtained, and differentially expressed (DE) mRNAs and lncRNAs between tumor and normal samples were identified. Univariate Cox and pathway enrichment analyses were performed on the m6A‐targeted lncRNAs and the LIHC prognosis‐related m6A‐targeted lncRNAs. Prognostic analysis, immune infiltration, and gene DE analyses were performed on LIHC subgroups, which were obtained from unsupervised clustering analysis. Additionally, a multi‐factor Cox analysis was used to construct a prognostic risk model based on the lncRNAs from the LASSO Cox model. Univariate and multivariate Cox analyses were used to assess prognostic independence.ResultsA total of 5031 significant DEmRNAs and 292 significant DElncRNAs were screened, and 72 LIHC‐specific m6A‐targeted binding lncRNAs were screened. Moreover, a total of 29 LIHC prognosis‐related m6A‐targeted lncRNAs were obtained and enriched in cytoskeletal, spliceosome, and cell cycle pathways. An 11‐m6A‐lncRNA prognostic model was constructed and verified; the top 10 lncRNAs included LINC00152, RP6‐65G23.3, RP11‐620J15.3, RP11‐290F5.1, RP11‐147L13.13, RP11‐923I11.6, AC092171.4, KB‐1460A1.5, LINC00339, and RP11‐119D9.1. Additionally, the two LIHC subgroups, Cluster 1 and Cluster 2, showed significant differences in the immune microenvironment, m6A enzyme genes, and prognosis of LIHC.ConclusionThe m6A‐lncRNA prognostic model accurately and effectively predicted the prognostic survival of LIHC. Immune cells, immune checkpoints (ICs), and m6A enzyme genes could act as novel therapeutic targets for LIHC.