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利用TCGA RNA测序数据通过生物信息学分析鉴定肝细胞癌中的关键基因和信号通路。

Identification of key genes and pathways by bioinformatics analysis with TCGA RNA sequencing data in hepatocellular carcinoma.

作者信息

Zhu Qiandong, Sun Yunpeng, Zhou Qingqing, He Qikuan, Qian Haixin

机构信息

Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.

出版信息

Mol Clin Oncol. 2018 Dec;9(6):597-606. doi: 10.3892/mco.2018.1728. Epub 2018 Sep 27.

DOI:10.3892/mco.2018.1728
PMID:30546887
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6256287/
Abstract

Improved insight into the molecular characteristics of hepatocellular carcinoma (HCC) is required to predict prognosis and to develop a new rationale for targeted therapeutic strategy. Bioinformatics methods, including functional enrichment and network analysis combined with survival analysis, are required to process a large volume of data to obtain further information on differentially expressed genes (DEGs). The RNA sequencing data related to HCC in The Cancer Genome Atlas (TCGA) database were analyzed to screen DEGs, which were separately submitted to perform gene enrichment analysis to identify gene sets and signaling pathways, and to construct a protein-protein interaction (PPI) network. Subsequently, hub genes were selected by the core level in the network, and the top hub genes were focused on gene expression analysis and survival analysis. A total of 610 DEGs were identified, including 444 upregulated and 166 downregulated genes. The upregulated DEGs were significantly enriched in the Gene Ontology analysis (GO): Cell division and in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway: Cell cycle, whereas the downregulated DEGs were enriched in GO: Negative regulation of growth and in the KEGG pathway: Retinol metabolism, with significant differences. Cyclin-dependent kinase (CDK)1 was selected as the top hub gene by the PPI network, which exhibited a similar expression trend with the data from the Gene Expression Omnibus (GEO) database. Survival analysis revealed a significantly negative correlation between CDK1 expression level and overall survival in the TCGA group (P<0.01) and the GEO group (P<0.01). Therefore, high-throughput TCGA data analysis appears to be an effective method for screening tumor molecular markers, and high expression of CDK1 is a prognostic factor for HCC.

摘要

为了预测肝细胞癌(HCC)的预后并为靶向治疗策略制定新的理论依据,需要更深入地了解其分子特征。需要运用生物信息学方法,包括功能富集和网络分析并结合生存分析,来处理大量数据,以获取有关差异表达基因(DEG)的更多信息。对癌症基因组图谱(TCGA)数据库中与HCC相关的RNA测序数据进行分析,以筛选DEG,分别将这些DEG进行基因富集分析,以确定基因集和信号通路,并构建蛋白质-蛋白质相互作用(PPI)网络。随后,通过网络中的核心水平选择枢纽基因,并将顶级枢纽基因重点用于基因表达分析和生存分析。共鉴定出610个DEG,其中包括444个上调基因和166个下调基因。上调的DEG在基因本体分析(GO)中显著富集于:细胞分裂,在京都基因与基因组百科全书(KEGG)通路中富集于:细胞周期;而下调的DEG在GO中富集于:生长的负调控,在KEGG通路中富集于:视黄醇代谢,差异显著。细胞周期蛋白依赖性激酶(CDK)1被PPI网络选为顶级枢纽基因,其表达趋势与基因表达综合数据库(GEO)的数据相似。生存分析显示,TCGA组(P<0.01)和GEO组(P<0.01)中CDK1表达水平与总生存期之间存在显著负相关。因此,高通量TCGA数据分析似乎是筛选肿瘤分子标志物的有效方法,CDK1的高表达是HCC的一个预后因素。

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