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

Abstract

Background Liver 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. Methods The 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. Results A 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. Conclusion The 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.

Effects of N6-Methyladenosine Modification on Cancer Progression: Molecular Mechanisms and Cancer Therapy

“…LincRNA-p21 acts as a tumor inhibitor in the development of esophageal squamous cell carcinoma ( 27 ). In hepatocellular carcinoma, the m 6 A methylation modification of LINC00152 is involved in the prognosis of LIHC patients through the cytoskeleton regulation pathway ( 28 ). Furthermore, in rectal cancer, m 6 A modification of lncRNA RP11 can upregulate the translation of Zeb1 to trigger cancer cell dissemination ( 29 ); lncRNA-THOR enhances IGF2BP1-targeted mRNA expression and promotes human osteosarcoma cell survival and proliferation ( 30 ).…”

The role of UCA1 and WRAP53 in diagnosis of hepatocellular carcinoma: A single-center case-control study

“…Long non-coding RNAs (lncRNAs), defined as noncoding RNA longer than 200 nucleotides [ 14 ], act as regulators in many physiological processes, such as the regulation of cell proliferation, differentiation and apoptosis [ 15 ]. Recently it was found that they play a critical role in oncogenesis, tumor suppression and invasion of different types of cancers, of which HCC was not an exception [ 16 ]. Fortunately, some HCC-related lncRNAs are present in serum in a stable measurable form, and thus are easy to detect and analyze; hence they have a good potential to be used as novel biomarkers for HCC.…”

A cuproptosis-related lncRNA signature for predicting prognosis and immune response in hepatocellular carcinoma

“…With the assistance of bioinformatics, the utilization of lncRNAs to construct models to predict prognosis and other phenotypes of cancer patients has achieved satisfactory results. For HCC, recent studies have described several lncRNA prognostic models related to different processes, such as ferroptosis, N-6 methylation, early recurrence, etc [11][12][13]. The study of lncRNAs related to cuproptosis contributes to a deeper understanding of cuproptosis and its function.…”