Identification of key genes and pathways in hepatocellular carcinoma A preliminary bioinformatics analysis

Identification of key genes and pathways in hepatocellular carcinoma A preliminary bioinformatics analysis
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DOI:
10.1097/md.0000000000014287
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发表时间:
2019-02-01
期刊:
影响因子:
1.6
通讯作者:
Li, Ning
Li, Ning
中科院分区:
医学4区
文献类型:
--
作者:
Wu, Min;Liu, Zhaobo;Li, Ning

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背景:肝细胞癌(HCC)是全世界最常见的癌症之一。然而,HCC发生和进展的确切机制仍不清楚。本研究试图通过综合生物信息学分析来识别和功能分析 HCC 和肝硬化组织之间的差异表达基因。方法:从基因表达综合库(GEO)下载GSE63898基因表达谱,并使用在线工具GEO2R进行分析,以识别差异表达基因(DEG)。 DEG 的基因本体(GO)功能分析和京都基因与基因组百科全书(KEGG)通路富集分析在 DAVID 中进行。使用 STRING 数据库评估 DEG 的相互作用,并使用 Cytoscape 软件构建蛋白质-蛋白质相互作用(PPI)网络。使用 cytoHubba 插件选择 Hub 基因,并使用 cBioPortal 数据库进行验证。结果:HCC 和肝硬化组织之间总共鉴定出 301 个 DEG。 GO分析结果表明,这些DEG在某些生物过程中显着富集,包括生长的负调节和细胞趋化性。包括 p53 信号通路在内的几个重要通路被确定与这些 DEG 密切相关。筛选出前12位的枢纽基因,包括TTK、NCAPG、TOP2A、CCNB1、CDK1、PRC1、RRM2、UBE2C、ZWINT、CDKN3、AURKA和RACGAP1。 cBioPortal 分析发现,中心基因的改变可能导致 HCC 的无病生存率显着降低。结论:本研究鉴定了一系列可能参与HCC致瘤和进展的关键基因和通路,为HCC致癌的潜在分子机制提供了新的认识。
Background: Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide. However, the precise mechanisms of the development and progression of HCC remain unclear. The present study attempted to identify and functionally analyze the differentially expressed genes between HCC and cirrhotic tissues by using comprehensive bioinformatics analyses. Methods: The GSE63898 gene expression profile was downloaded from the Gene Expression Omnibus (GEO) and analyzed using the online tool GEO2R to identify differentially expressed genes (DEGs). Gene ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEGs were performed in DAVID. The STRING database was used to evaluate the interactions of DEGs and to construct a protein-protein interaction (PPI) network using Cytoscape software. Hub genes were selected using the cytoHubba plugin and were validated with the cBioPortal database. Results: A total of 301 DEGs were identified between HCC and cirrhotic tissues. The GO analysis results showed that these DEGs were significantly enriched in certain biological processes including negative regulation of growth and cell chemotaxis. Several significant pathways, including the p53 signaling pathway, were identified as being closely associated with these DEGs. The top 12 hub genes were screened and included TTK, NCAPG, TOP2A, CCNB1, CDK1, PRC1, RRM2, UBE2C, ZWINT, CDKN3, AURKA, and RACGAP1. The cBioPortal analysis found that alterations in hub genes could result in significantly reduced disease-free survival in HCC. Conclusion: The present study identified a series of key genes and pathways that may be involved in the tumorigenicity and progression of HCC, providing a new understanding of the underlying molecular mechanisms of carcinogenesis in HCC.