基因芯片筛选肝细胞性肝癌的差异表达基因和通路

Identification of differentially expressed genes and pathways in hepatocellular carcinoma by using microarray

目的 通过基因芯片和生物信息学的分析方法,筛选与肝癌发病相关的差异表达基因和通路,为进一步研究肝癌发生发展过程中的相关机制提供依据。方法 收集2对肝癌组织和对应的癌旁组织,提取总RNA,并与基因芯片行杂交检测,分析得到差异表达基因。使用DAVID数据库,对差异基因行GO功能注释和KEGG富集分析;应用String蛋白互作数据库分析差异表达基因的蛋白互作关系,构建蛋白互作网络并通过Cytoscape行可视化分析,运用网络分析插件CytoHubba筛选核心基因,最后结合TCGA (The Cancer Genome Atlas)数据库中肝癌基因表达数据,初步探究核心基因在肝癌中的表达情况。结果 按设定的标准,共筛选得到4 324个差异表达基因,上调表达的有2 552个,下调表达的有1 772个。GO分析显示差异基因主要参与血小板衍生生长因子结合、受体抑制剂和拮抗剂活性等相关的分子功能;KEGG富集分析提示这些基因与TGF-β、Rap1、PI3K-Akt以及趋化因子等信号通路相关。蛋白互作网络分析筛选得到6个核心基因,TCGA数据库验证发现核心基因DCN、COL1A1和COL1A2在肝癌组织中的表达存在显著差异(P<0.000 1)。结论 GO功能注释和KEGG富集分析揭示了肝癌潜在的发病机制,核心基因为肝癌的研究提供新方向,有可能成为肝癌诊断和治疗的潜在靶点。

Objective To further investigate the pathogenesis of hepatocellular carcinoma(HCC),we screened the differentially expressed genes and pathways by using microarray and bioinformatics analysis method.Methods The microarray data of 2 pairs HCC tumor tissues and corresponding adjacent normal tissues were and to analyze differentially expressed genes(DEGs).GO functional and KEGG enrichment analysis for DEGs were performed to use DAVID database.The protein-protein interaction(PPI)network was constructed by the String protein interaction database.In addition,the PPI network was visualized by Cytoscape,and the hub genes were screened by using CytoHubba App.Finally,we preliminarily investigated the hub genes expression in HCC by analyzing the RNA-sequencing data deposited in The Cancer Genome Atlas(TCGA).Results According to the established standard,we identified 4 324 DEGs including 2 552 up-regulated genes and 1 772 down-regulated genes.GO analysis showed that DEGs were mainly involved in the platelet-derived growth factor binding(PDGF),receptor inhibitor and antagonist activity;KEGG enrichment analysis indicated that these genes were related to TGF-β,Rap1,PI3 K-Akt,and chemokine signaling pathway.Six hub genes related to HCC were screened from PPI network.Moreover,there were significantly differences in the hub genes expression of DCN,COL1 A1,and COL1 A2 in HCC tissues confirmed by the analysis of TCGA database(P<0.000 1).Conclusion GO functional and KEGG enrichment analysis may reveal the potential pathogenesis of HCC.The hub genes provide new clues for the research of HCC,and may become potential targets for the diagnosis and treatment of HCC.