Analysis of m6A RNA Methylation-Related Genes in Liver Hepatocellular Carcinoma and Their Correlation with Survival

Abstract

N6-methyladenosine (m6A) modification on RNA plays an important role in tumorigenesis and metastasis, which could change gene expression and even function at multiple levels such as RNA splicing, stability, translocation, and translation. In this study, we aim to conduct a comprehensive analysis on m6A RNA methylation-related genes, including m6A RNA methylation regulators and m6A RNA methylation-modified genes, in liver hepatocellular carcinoma, and their relationship with survival and clinical features. Data, which consist of the expression of widely reported m6A RNA methylation-related genes in liver hepatocellular carcinoma from The Cancer Genome Atlas (TCGA), were analyzed by one-way ANOVA, Univariate Cox regression, a protein–protein interaction network, gene enrichment analysis, feature screening, a risk prognostic model, correlation analysis, and consensus clustering analysis. In total, 405 of the m6A RNA methylation-related genes were found based on one-way ANOVA. Among them, DNA topoisomerase 2-alpha (TOP2A), exodeoxyribonuclease 1 (EXO1), ser-ine/threonine-protein kinase Nek2 (NEK2), baculoviral IAP repeat-containing protein 5 (BIRC5), hyaluronan mediated motility receptor (HMMR), structural maintenance of chromosomes protein 4 (SMC4), bloom syndrome protein (BLM), ca-sein kinase I isoform epsilon (CSNK1E), cytoskeleton-associated protein 5 (CKAP5), and inner centromere protein (INCENP), which were m6A RNA methylation-modified genes, were recognized as the hub genes based on the protein–protein interaction analysis. The risk prognostic model showed that gender, AJCC stage, grade, T, and N were significantly different between the subgroup with the high and low risk groups. The AUC, the evaluation parameter of the prediction model which was built by RandomForest, was 0.7. Furthermore, two subgroups were divided by consensus clustering analysis, in which stage, grade, and T differed. We identified the important genes expressed significantly among two clusters, including uridine-cytidine kinase 2 (UCK2), filensin (BFSP1), tubulin-specific chaperone D (TBCD), histone-lysine N-methyltransferase PRDM16 (PRDM16), phosphorylase b ki-nase regulatory subunit alpha (PHKA2), serine/threonine-protein kinase BRSK2 (BRSK2), Arf-GAP with coiled-coil (ACAP3), general transcription factor 3C polypep-tide 2 (GTF3C2), and guanine nucleotide exchange factor MSS4 (RABIF). In our study, the m6A RNA methylation-related genes in liver hepatocellular carcinoma were analyzed systematically, including the expression, interaction, function, and prognostic values, which provided an important theoretical basis for m6A RNA methylation in liver cancer. The nine important m6A-related genes could be prognostic markers in the survival time of patients.

METTL3 Intensifies the Progress of Oral Squamous Cell Carcinoma via Modulating the m6A Amount of PRMT5 and PD-L1

“…Methylation in the 5 ′ UTR region of mRNA plays an important part in mRNA degradation, stability, editing, splicing, polyadenylation, etc. Methylation in the 3 ′ UTR region makes contribution to exonuclear transport of mRNA, structural stability of mRNA with polyA-binding proteins, and initiation of translation [31][32][33]. We hypothesized that METTL3 may mediate the methylation of PRMT5 mRNA and participate in the pathogenesis of OSCC.…”

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

“…. An increasing number of reports have confirmed the pathological significance of m 6 A in cancers, including LIHC 32 …”

Identification and Validation of an Immune-Related eRNA Prognostic Signature for Hepatocellular Carcinoma

“…Moreover, the risk gene AL445524.1 was demonstrated to be associated significantly with poor prognosis of OS and immunerelated genes including RABIF, CYTOR, CCT3, NME1, and KRTCAP2. The RABIF has been identified to be a biomarker candidate of breast cancer development (Switnicki et al, 2016) and associated with HCC (Li et al, 2021). The CYTOR has been reported being upregulated in many cancers, including HCC, lung adenocarcinoma, and renal cell carcinoma (Liang et al, 2018).…”