scholarly journals N6-methyladenosine (m6A) RNA methylation regulators are associated with clinical prognosis in hepatocellular carcinoma

2020 ◽  
Vol 9 (1) ◽  
pp. 323-334
Author(s):  
Gao Li ◽  
Yue Zhang ◽  
Xiaowei Du ◽  
Wanjun Li ◽  
Yanming Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Prognosis ◽  
Rna Methylation ◽  
M6a Rna Methylation

scholarly journals Multiple m6A RNA methylation modulators promote the malignant progression of hepatocellular carcinoma and affect its clinical prognosis

2020 ◽  
Author(s):  
Nanfang Qu ◽  
Sanyu Qin ◽  
Xuemei Zhang ◽  
Xiaotong Bo ◽  
Zhengchun Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Genome ◽  
Malignant Progression ◽  
World Health ◽  
Pathological Grade ◽  
Clinical Prognosis ◽  
Rna Methylation ◽  
Expression Levels ◽  
Normal Tissues ◽  
M6a Rna Methylation

Abstract Background: Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death in the world. N 6 -methyladenosine (m 6 A) RNA methylation is dynamically regulated by m 6 A RNA methylation modulators (“writer,” “eraser,” and “reader” proteins), which are associated with cancer occurrence and development. The purpose of this study was to explore the relationships between m 6 A RNA methylation modulators and HCC. Methods: First, using data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, we compared the expression levels of 13 major m6A RNA methylation modulators between HCC and normal tissues. Second, we applied consensus clustering to the expression data on the m 6 A RNA methylation modulators to divide the HCC tissues into two subgroups (clusters 1 and 2), and we compared the clusters in terms of overall survival (OS), World Health Organization (WHO) stage, and pathological grade. Third, using least absolute shrinkage and selection operator (LASSO) regression, we constructed a risk signature involving the m 6 A RNA methylation modulators that affected OS in TCGA and ICGC analyses. Results: We found that the expression levels of 12 major m6A RNA methylation modulators were significantly different between HCC and normal tissues. After dividing the HCC tissues into clusters 1 and 2, we found that cluster 2 had poorer OS, higher WHO stage, and higher pathological grade. Four m 6 A RNA methylation modulators (YTHDF1, YTHDF2, METTL3, and KIAA1429) affecting OS in the TCGA and ICGC analyses were selected to construct a risk signature, which was significantly associated with WHO stage and was also an independent prognostic marker of OS. Conclusions: In summary, m 6 A RNA methylation modulators are key participants in the malignant progression of HCC and have potential value in prognostication and treatment decisions.

scholarly journals Multiple m6A RNA methylation modulators promote the malignant progression of hepatocellular carcinoma and affect its clinical prognosis

2019 ◽  
Author(s):  
Nanfang Qu ◽  
Haixing Jiang ◽  
Sanyu Qin ◽  
Xuemei Zhang ◽  
Zhengchun Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Genome ◽  
Malignant Progression ◽  
World Health ◽  
Pathological Grade ◽  
Clinical Prognosis ◽  
Rna Methylation ◽  
Expression Levels ◽  
Normal Tissues ◽  
M6a Rna Methylation

Abstract Background: Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death in the world. N 6 -methyladenosine (m 6 A) RNA methylation is dynamically regulated by m 6 A RNA methylation modulators (“writer,” “eraser,” and “reader” proteins), which are associated with cancer occurrence and development. The purpose of this study was to explore the relationships between m 6 A RNA methylation modulators and HCC. Methods: First, using data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, we compared the expression levels of 13 major m6A RNA methylation modulators between HCC and normal tissues. Second, we applied consensus clustering to the expression data on the m 6 A RNA methylation modulators to divide the HCC tissues into two subgroups (clusters 1 and 2), and we compared the clusters in terms of overall survival (OS), World Health Organization (WHO) stage, and pathological grade. Third, using least absolute shrinkage and selection operator (LASSO) regression, we constructed a risk signature involving the m 6 A RNA methylation modulators that affected OS in TCGA and ICGC analyses. Results: We found that the expression levels of 12 major m6A RNA methylation modulators were significantly different between HCC and normal tissues. After dividing the HCC tissues into clusters 1 and 2, we found that cluster 2 had poorer OS, higher WHO stage, and higher pathological grade. Four m 6 A RNA methylation modulators (YTHDF1, YTHDF2, METTL3, and KIAA1429) affecting OS in the TCGA and ICGC analyses were selected to construct a risk signature, which was significantly associated with WHO stage and was also an independent prognostic marker of OS. Conclusions: In summary, m 6 A RNA methylation modulators are key participants in the malignant progression of HCC and have potential value in prognostication and treatment decisions.

scholarly journals Multiple m6A RNA methylation modulators promote the malignant progression of hepatocellular carcinoma and affect its clinical prognosis

2020 ◽  
Author(s):  
Nanfang Qu ◽  
Sanyu Qin ◽  
Xuemei Zhang ◽  
Xiaotong Bo ◽  
Zhengchun Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Genome ◽  
Malignant Progression ◽  
World Health ◽  
Pathological Grade ◽  
Clinical Prognosis ◽  
Rna Methylation ◽  
Expression Levels ◽  
Normal Tissues ◽  
M6a Rna Methylation

Abstract Background: Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death in the world. N 6 -methyladenosine (m 6 A) RNA methylation is dynamically regulated by m 6 A RNA methylation modulators (“writer,” “eraser,” and “reader” proteins), which are associated with cancer occurrence and development. The purpose of this study was to explore the relationships between m 6 A RNA methylation modulators and HCC. Methods: First, using data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, we compared the expression levels of 13 major m6A RNA methylation modulators between HCC and normal tissues. Second, we applied consensus clustering to the expression data on the m 6 A RNA methylation modulators to divide the HCC tissues into two subgroups (clusters 1 and 2), and we compared the clusters in terms of overall survival (OS), World Health Organization (WHO) stage, and pathological grade. Third, using least absolute shrinkage and selection operator (LASSO) regression, we constructed a risk signature involving the m 6 A RNA methylation modulators that affected OS in TCGA and ICGC analyses. Results: We found that the expression levels of 12 major m6A RNA methylation modulators were significantly different between HCC and normal tissues. After dividing the HCC tissues into clusters 1 and 2, we found that cluster 2 had poorer OS, higher WHO stage, and higher pathological grade. Four m 6 A RNA methylation modulators (YTHDF1, YTHDF2, METTL3, and KIAA1429) affecting OS in the TCGA and ICGC analyses were selected to construct a risk signature, which was significantly associated with WHO stage and was also an independent prognostic marker of OS. Conclusions: In summary, m 6 A RNA methylation modulators are key participants in the malignant progression of HCC and have potential value in prognostication and treatment decisions.

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

2021 ◽  
Vol 22 (3) ◽  
pp. 1474
Author(s):  
Yong Li ◽  
Dandan Qi ◽  
Baoli Zhu ◽  
Xin Ye
Keyword(s):  
Hepatocellular Carcinoma ◽  
Protein Kinase ◽  
Clustering Analysis ◽  
Prognostic Model ◽  
Consensus Clustering ◽  
Rna Methylation ◽  
Protein Protein Interaction ◽  
M6a Rna Methylation ◽  
Liver Hepatocellular Carcinoma ◽  
One Way Anova

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.

scholarly journals Expression pattern and prognostic value of N6-methyladenosine RNA methylation key regulators in hepatocellular carcinoma

Mutagenesis ◽  
2021 ◽  
Vol 36 (5) ◽  
pp. 369-379
Author(s):  
Min Deng ◽  
Lin Fang ◽  
Shao-Hua Li ◽  
Rong-Ce Zhao ◽  
Jie Mei ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Risk Score ◽  
Critical Role ◽  
Risk Groups ◽  
High Risk Group ◽  
The Cancer Genome Atlas ◽  
Consensus Clustering ◽  
Rna Methylation ◽  
M6a Rna Methylation

Abstract Hepatocellular carcinoma (HCC) is still one of the most common malignancies worldwide. The accuracy of biomarkers for predicting the prognosis of HCC and the therapeutic effect is not satisfactory. N6-methyladenosine (m6A) methylation regulators play a crucial role in various tumours. Our research aims further to determine the predictive value of m6A methylation regulators and establish a prognostic model for HCC. In this study, the data of HCC from The Cancer Genome Atlas (TCGA) database was obtained, and the expression level of 15 genes and survival was examined. Then we identified two clusters of HCC with different clinical factors, constructed prognostic markers and analysed gene set enrichment, proteins’ interaction and gene co-expression. Three subgroups by consensus clustering according to the expression of the 13 genes were identified. The risk score generated by five genes divided HCC patients into high-risk and low-risk groups. In addition, we developed a prognostic marker that can identify high-risk HCC. Finally, a novel prognostic nomogram was developed to accurately predict HCC patients’ prognosis. The expression levels of 13 m6A RNA methylation regulators were significantly upregulated in HCC samples. The prognosis of cluster 1 and cluster 3 was worse. Patients in the high-risk group show a poor prognosis. Moreover, the risk score was an independent prognostic factor for HCC patients. In conclusion, we reveal the critical role of m6A RNA methylation modification in HCC and develop a predictive model based on the m6A RNA methylation regulators, which can accurately predict HCC patients’ prognosis and provide meaningful guidance for clinical treatment.

scholarly journals m6A RNA Methylation Regulators Elicit Malignant Progression and Predict Clinical Outcome in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Wenli Li ◽  
Jun Liu ◽  
Zhanzhong Ma ◽  
Xiaofeng Zhai ◽  
Binbin Cheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cell ◽  
Clinical Outcome ◽  
Cox Regression ◽  
Expression Profiles ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Rna Methylation ◽  
M6a Rna Methylation

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and N6-methyladenosine (m6A) is a predominant internal modification of RNA in various cancers. We obtained the expression profiles of m6A-related genes for HCC patients from the International Cancer Genome Consortium and The Cancer Genome Atlas datasets. Most of the m6A RNA methylation regulators were confirmed to be differentially expressed among groups stratified by clinical characteristics and tissues. The clinical factors (including stage, grade, and gender) were correlated with the two subgroups (cluster 1/2). We identified an m6A RNA methylation regulator-based signature (including METTL3, YTHDC2, and YTHDF2) that could effectively stratify a high-risk subset of these patients by univariate and LASSO Cox regression, and receiver operating characteristic (ROC) analysis indicated that the signature had a powerful predictive ability. Immune cell analysis revealed that the genes in the signature were correlated with B cell, CD4 T cell, CD8 T cell, dendritic cell, macrophage, and neutrophil. Functional enrichment analysis suggested that these three genes may be involved in genetic and epigenetic events with known links to HCC. Moreover, the nomogram was established based on the signature integrated with clinicopathological features. The calibration curve and the area under ROC also demonstrated the good performance of the nomogram in predicting 3- and 5-year OS in the ICGC and TCGA cohorts. In summary, we demonstrated the vital role of m6A RNA methylation regulators in the initial presentation and progression of HCC and constructed a nomogram which would predict the clinical outcome and provide a basis for individualized therapy.

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