基于生物信息学对NK细胞抑制肝细胞癌发生发展潜在关键基因的筛选和鉴定

Screening and identification of potential key genes of NK cells in inhibiting development and progression of hepatocellular carcinoma based on bioinformatics

目的基于生物信息学探讨和筛选自然杀伤(NK)细胞抑制肝细胞癌(HCC)发生发展过程中的关键基因及相关的信号通路。方法在美国国立生物技术信息中心公共数据平台基因表达组学数据库(GEO)下载基因芯片数据GSE120123,从中选取4个关于NK细胞的样本,其中2个样本来自正常肝组织,2个来自HCC组织。分析其差异表达基因(DEGs),输入DAVID数据库进行基因本体学(GO)及京都基因和基因组百科全书(KEGG)分析,用Cyto⁃scape软件构建蛋白质—蛋白质相互作用(PPI)网络,并利用STRING和Cytoscape进行模块分析,通过CytoHubba插件筛选关键基因。结果共鉴定出317个DEGs(218个下调基因及99个上调基因)。GO及KEGG分析结果表明,白细胞细胞黏附、RNA聚合酶Ⅱ启动子转录的负调控、细胞黏附分子、Rap1信号传导途径、细胞因子—细胞因子受体相互作用、趋化因子信号传导等信号途径参与到NK细胞抑制HCC的发生发展过程中。PPI网络由268个节点和242个边组成。最终选择出4个关键基因:CCR1、CCR5、CXCR6和CXCL12。结论NK细胞抑制HCC发生发展过程中的潜在关键基因为CCR1、CCR5、CXCR6和CXCL12。

Objective To investigate and screen key genes and related signaling pathways in the process of natural killer(NK)cells inhibiting the development and progression of hepatocellular carcinoma(HCC).Methods The gene microarray data GSE120123 was downloaded from the National Center for Biotechnology Information(NCBI)database Gene Expression Omnibus(GEO),and we selected 4 samples of NK cells,2 of which were from normal liver tissues and 2 of which were from HCC tissues.The differentially expressed genes(DEGs)were analyzed and were input into the DAVID database for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)functional enrichment analysis,and we constructed protein-protein interaction using Cytoscape software.Module analysis was also performed using STRING and Cytoscape.Finally,the key genes were selected by CytoHubba plug-in.Results A total of 317 DEGs(218 down-regulated genes and 99 up-regulated genes)were identified.GO and KEGG analysis showed that,leukocyte cell adhesion,negative regulation of RNA polymerase Ⅱ promoter transcription,cytosolic adhesion molecules,Rap1 signaling pathway,cytokine-cytokine receptor interaction,chemokine signaling and other signaling pathways were found to be involved in the inhibition of development and progression of HCC by NK cells.The PPI network consisted of 268 nodes and 242 edges.Finally,4 key genes were screened out,including CCR1,CCR5,CXCR6,and CXCL12.Conclusion CCR1,CCR5,CXCR6,and CXCL12 were key potential key genes of NK cells in inhibiting development and progression of HCC.