DNA methylation biomarkers for hepatocellular carcinoma.
DNA methylation biomarkers for hepatocellular carcinoma.
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DOI：
10.1186/s12935-018-0629-5
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发表时间：
2018
影响因子：
5.8
通讯作者：
Cai X
中科院分区：
文献类型：
--
作者：
Fan G;Tu Y;Chen C;Sun H;Wan C;Cai X
DNA甲基化异常是导致肝细胞癌的关键因素。在这项研究中，我们试图整合四个队列资料数据集，以确定与肝癌相关的异常甲基化基因和途径。为此，我们从GEO数据库下载了检测基因表达(GSE84402，GSE46408)和基因甲基化(GSE73003，GSE57956)的微阵列数据集。对异常甲基化差异表达基因(Deg)进行分类和通路分析。然后使用字符串数据库对已识别的途径和基因进行丰富和功能分析。用Cytoscape软件建立蛋白质-蛋白质相互作用网络，用MCODE进行模块分析。最后，利用OncoLnc在线工具对HUB基因进行总体生存分析。在筛选阶段，我们总共鉴定了19个低甲基化的高表达基因和14个高甲基化的低表达基因，最终发现了6个变化最大的HUB基因，包括MAD2L1、CDC20、CCNB1、CCND1、AR和ESR1。通路分析显示，在肝细胞癌中，异常甲基化主要与细胞周期过程、P53信号和MAPK信号有关。在TCGA数据库中验证后，HUB基因的甲基化和表达状态发生了显著变化，与我们的结果一致。MAD2L1、CDC20和CCNB1高表达而CCND1、AR和ESR1低表达的患者总生存期较短。综上所述，我们已经发现了与肝癌相关的新的异常甲基化基因和通路，可能为控制肝癌进展的分子机制提供新的见解，并作为精确诊断和疾病治疗的新生物标志物。本文的在线版本(10.1186/s12935-0180629-5)包含补充材料，授权用户可以使用。
Aberrant methylation of DNA is a key driver of hepatocellular carcinoma (HCC). In this study, we sought to integrate four cohorts profile datasets to identify such abnormally methylated genes and pathways associated with HCC. To this end, we downloaded microarray datasets examining gene expression (GSE84402, GSE46408) and gene methylation (GSE73003, GSE57956) from the GEO database. Abnormally methylated differentially expressed genes (DEGs) were sorted and pathways were analyzed. The String database was then used to perform enrichment and functional analysis of identified pathways and genes. Cytoscape software was used to create a protein–protein interaction network, and MCODE was used for module analysis. Finally, overall survival analysis of hub genes was performed by the OncoLnc online tool. In total, we identified 19 hypomethylated highly expressed genes and 14 hypermethylated lowly expressed genes at the screening step, and finally found six mostly changed hub genes including MAD2L1, CDC20, CCNB1, CCND1, AR and ESR1. Pathway analysis showed that aberrantly methylated-DEGs mainly associated with the cell cycle process, p53 signaling, and MAPK signaling in HCC. After validation in TCGA database, the methylation and expression status of hub genes was significantly altered and same with our results. Patients with high expression of MAD2L1, CDC20 and CCNB1 and low expression of CCND1, AR, and ESR1 was associated with shorter overall survival. Taken together, we have identified novel aberrantly methylated genes and pathways linked to HCC, potentially offering novel insights into the molecular mechanisms governing HCC progression and serving as novel biomarkers for precision diagnosis and disease treatment. The online version of this article (10.1186/s12935-018-0629-5) contains supplementary material, which is available to authorized users.
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