Analysis of m6A RNA Methylation-Related Genes in Liver Hepatocellular Carcinoma and Their Correlation with Survival
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...
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doaj-4e777675cd5043efa0a393362e56cdd32021-02-03T00:03:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01221474147410.3390/ijms22031474Analysis of m6A RNA Methylation-Related Genes in Liver Hepatocellular Carcinoma and Their Correlation with SurvivalYong Li0Dandan Qi1Baoli Zhu2Xin Ye3Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, ChinaSavaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, ChinaKey Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, ChinaKey Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, ChinaN6-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 (<i>TOP2A</i>), exodeoxyribonuclease 1 (<i>EXO1</i>), ser-ine/threonine-protein kinase Nek2 (<i>NEK2</i>), baculoviral IAP repeat-containing protein 5 (<i>BIRC5</i>), hyaluronan mediated motility receptor (<i>HMMR</i>), structural maintenance of chromosomes protein 4 (SMC4), bloom syndrome protein (<i>BLM</i>), ca-sein kinase I isoform epsilon (<i>CSNK1E</i>), cytoskeleton-associated protein 5 (<i>CKAP5</i>), and inner centromere protein (<i>INCENP</i>), 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 (<i>UCK2</i>), filensin (<i>BFSP1</i>), tubulin-specific chaperone D (<i>TBCD</i>), histone-lysine N-methyltransferase PRDM16 (<i>PRDM16</i>), phosphorylase b ki-nase regulatory subunit alpha (<i>PHKA2</i>), serine/threonine-protein kinase BRSK2 (<i>BRSK2</i>), Arf-GAP with coiled-coil (<i>ACAP3</i>), general transcription factor 3C polypep-tide 2 (<i>GTF3C2</i>), and guanine nucleotide exchange factor MSS4 (<i>RABIF</i>). 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.https://www.mdpi.com/1422-0067/22/3/1474m6A modificationm6A related genessurvivalliver cancerTCGA |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yong Li Dandan Qi Baoli Zhu Xin Ye |
spellingShingle |
Yong Li Dandan Qi Baoli Zhu Xin Ye Analysis of m6A RNA Methylation-Related Genes in Liver Hepatocellular Carcinoma and Their Correlation with Survival International Journal of Molecular Sciences m6A modification m6A related genes survival liver cancer TCGA |
author_facet |
Yong Li Dandan Qi Baoli Zhu Xin Ye |
author_sort |
Yong Li |
title |
Analysis of m6A RNA Methylation-Related Genes in Liver Hepatocellular Carcinoma and Their Correlation with Survival |
title_short |
Analysis of m6A RNA Methylation-Related Genes in Liver Hepatocellular Carcinoma and Their Correlation with Survival |
title_full |
Analysis of m6A RNA Methylation-Related Genes in Liver Hepatocellular Carcinoma and Their Correlation with Survival |
title_fullStr |
Analysis of m6A RNA Methylation-Related Genes in Liver Hepatocellular Carcinoma and Their Correlation with Survival |
title_full_unstemmed |
Analysis of m6A RNA Methylation-Related Genes in Liver Hepatocellular Carcinoma and Their Correlation with Survival |
title_sort |
analysis of m6a rna methylation-related genes in liver hepatocellular carcinoma and their correlation with survival |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-02-01 |
description |
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 (<i>TOP2A</i>), exodeoxyribonuclease 1 (<i>EXO1</i>), ser-ine/threonine-protein kinase Nek2 (<i>NEK2</i>), baculoviral IAP repeat-containing protein 5 (<i>BIRC5</i>), hyaluronan mediated motility receptor (<i>HMMR</i>), structural maintenance of chromosomes protein 4 (SMC4), bloom syndrome protein (<i>BLM</i>), ca-sein kinase I isoform epsilon (<i>CSNK1E</i>), cytoskeleton-associated protein 5 (<i>CKAP5</i>), and inner centromere protein (<i>INCENP</i>), 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 (<i>UCK2</i>), filensin (<i>BFSP1</i>), tubulin-specific chaperone D (<i>TBCD</i>), histone-lysine N-methyltransferase PRDM16 (<i>PRDM16</i>), phosphorylase b ki-nase regulatory subunit alpha (<i>PHKA2</i>), serine/threonine-protein kinase BRSK2 (<i>BRSK2</i>), Arf-GAP with coiled-coil (<i>ACAP3</i>), general transcription factor 3C polypep-tide 2 (<i>GTF3C2</i>), and guanine nucleotide exchange factor MSS4 (<i>RABIF</i>). 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. |
topic |
m6A modification m6A related genes survival liver cancer TCGA |
url |
https://www.mdpi.com/1422-0067/22/3/1474 |
work_keys_str_mv |
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