Bioinformatics analysis of aberrantly methylated-differentially expressed genes and pathways in hepatocellular carcinoma.
Bioinformatics analysis of aberrantly methylated-differentially expressed genes and pathways in hepatocellular carcinoma.
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DOI：
10.3748/wjg.v24.i24.2605
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发表时间：
2018-06-28
影响因子：
4.3
通讯作者：
Zhao WJ
中科院分区：
文献类型：
--
作者：
Sang L;Wang XM;Xu DY;Zhao WJ
发现肝细胞癌（HCC）中甲基化差异表达基因（MDEG），探索相关枢纽基因和潜在途径。GSE 25097和GSE 57956的表达谱数据来自GEO数据集。我们使用GEO 2 R在线分析差异甲基化基因和差异表达基因。使用大卫数据库进行MDEG的功能和富集分析。蛋白质-蛋白质相互作用（PPI）网络由STRING执行，然后在Cytoscape中可视化。通过cytoHubba对Hub基因进行排序，并通过Cytoscape软件中的MCODE对PPI网络进行模块分析。总之，我们将266个基因归类为高甲基化低表达基因（Hyper-LGs），涉及内源性和激素刺激，细胞表面受体相关的信号转导和行为。此外，161个基因被标记为低甲基化，高表达基因（Hypo-HGs），涉及DNA复制和代谢过程，细胞周期和分裂。通路分析表明，Hyper-LGs富集于癌症、Wnt和趋化因子信号通路，而Hypo-HGs与细胞周期和类固醇激素生物合成通路相关。基于PPI网络，结合cytoHubba的6种排序方法，将PTGS 2、PIK 3CD、CXCL 1、ESR 1和MMP 2确定为Hyper-LG的枢纽基因，将CDC 45、DTL、AURKB、CDKN 3、MCM 2和MCM 10确定为Hypo-HG的枢纽基因。在这项研究中，我们揭示了许多新的遗传和表观遗传调控，并提供了一个重要的分子基础，以了解肝癌的发病机制。Hub基因包括PTGS 2、PIK 3CD、CXCL 1、ESR 1、MMP 2、CDC 45、DTL、AURKB、CDKN 3、MCM 2和MCM 10，可以作为基于异常甲基化的生物标志物用于HCC的准确诊断和治疗。
To discover methylated-differentially expressed genes (MDEGs) in hepatocellular carcinoma (HCC) and to explore relevant hub genes and potential pathways. The data of expression profiling GSE25097 and methylation profiling GSE57956 were gained from GEO Datasets. We analyzed the differentially methylated genes and differentially expressed genes online using GEO2R. Functional and enrichment analyses of MDEGs were conducted using the DAVID database. A protein-protein interaction (PPI) network was performed by STRING and then visualized in Cytoscape. Hub genes were ranked by cytoHubba, and a module analysis of the PPI network was conducted by MCODE in Cytoscape software. In total, we categorized 266 genes as hypermethylated, lowly expressed genes (Hyper-LGs) referring to endogenous and hormone stimulus, cell surface receptor linked signal transduction and behavior. In addition, 161 genes were labelled as hypomethylated, highly expressed genes (Hypo-HGs) referring to DNA replication and metabolic process, cell cycle and division. Pathway analysis illustrated that Hyper-LGs were enriched in cancer, Wnt, and chemokine signalling pathways, while Hypo-HGs were related to cell cycle and steroid hormone biosynthesis pathways. Based on PPI networks, PTGS2, PIK3CD, CXCL1, ESR1, and MMP2 were identified as hub genes for Hyper-LGs, and CDC45, DTL, AURKB, CDKN3, MCM2, and MCM10 were hub genes for Hypo-HGs by combining six ranked methods of cytoHubba. In the study, we disclose numerous novel genetic and epigenetic regulations and offer a vital molecular groundwork to understand the pathogenesis of HCC. Hub genes, including PTGS2, PIK3CD, CXCL1, ESR1, MMP2, CDC45, DTL, AURKB, CDKN3, MCM2, and MCM10, can be used as biomarkers based on aberrant methylation for the accurate diagnosis and treatment of HCC.
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