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基于DNA甲基化的急性髓系白血病患者预后生物标志物

DNA methylation-based prognostic biomarkers of acute myeloid leukemia patients.

作者信息

Hu Linjun, Gao Yuling, Shi Zhan, Liu Yang, Zhao Junjun, Xiao Zunqiang, Lou Jiayin, Xu Qiuran, Tong Xiangmin

机构信息

The Medical College of Qingdao University, Qingdao 266071, China.

Department of Genetic Laboratory, Shaoxing Women and Children Hospital, Shaoxing 312030, China.

出版信息

Ann Transl Med. 2019 Dec;7(23):737. doi: 10.21037/atm.2019.11.122.

Abstract

BACKGROUND

Acute myeloid leukemia (AML) is a heterogeneous clonal disease that prevents normal myeloid differentiation with its common features. Its incidence increases with age and has a poor prognosis. Studies have shown that DNA methylation and abnormal gene expression are closely related to AML.

METHODS

The methylation array data and mRNA array data are from the Gene Expression Omnibus (GEO) database. Through the GEO data, we identified differential genes from tumors and normal samples. Then we performed Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses on these differential genes. Protein-protein interaction (PPI) network construction and module analysis were performed to screen the highest-scoring modules. Next, we used SurvExpress software to analyze the genes in the highest-scoring module and selected potential prognostic genes by univariate and multivariate Cox analysis. Finally, the three genes screened by SurvExpress software were analyzed using the methylation analysis site MethSurv to explore AML associated methylation biomarkers.

RESULTS

We found three genes that can be used as independent prognostic factors for AML. These three genes are the low expression/methylation genes ATP11A and ITGAM, and the high expression/low methylation gene ZNRF2.

CONCLUSIONS

In this study, we performed a comprehensive analysis of DNA methylation and gene expression to identify key epigenetic genes in AML.

摘要

背景

急性髓系白血病(AML)是一种异质性克隆性疾病,其具有阻止正常髓系分化的共同特征。其发病率随年龄增长而增加,预后较差。研究表明,DNA甲基化和基因异常表达与AML密切相关。

方法

甲基化芯片数据和mRNA芯片数据来自基因表达综合数据库(GEO)。通过GEO数据,我们从肿瘤样本和正常样本中鉴定出差异基因。然后,我们对这些差异基因进行京都基因与基因组百科全书(KEGG)和基因本体论(GO)分析。进行蛋白质-蛋白质相互作用(PPI)网络构建和模块分析以筛选得分最高的模块。接下来,我们使用SurvExpress软件分析得分最高模块中的基因,并通过单变量和多变量Cox分析选择潜在的预后基因。最后,使用甲基化分析网站MethSurv对SurvExpress软件筛选出的三个基因进行分析,以探索与AML相关的甲基化生物标志物。

结果

我们发现了三个可作为AML独立预后因素的基因。这三个基因是低表达/甲基化基因ATP11A和ITGAM,以及高表达/低甲基化基因ZNRF2。

结论

在本研究中,我们对DNA甲基化和基因表达进行了综合分析,以鉴定AML中的关键表观遗传基因。

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