多个GEO芯片联合分析筛选鼻咽癌易感基因

Differential analysis of gene expression profiles of nasopharyngeal carcinoma based on a combined analysis of multiple GEO chip databases

目的:筛选鼻咽癌的关键基因,探讨鼻咽癌发病机制。方法:从公共基因芯片数据库(GEO)搜索有关鼻咽癌表达的数据,联合R语言分析鼻咽癌组织与正常鼻咽组织差异表达的基因;利用基因本体(GO)数据库和京都基因与基因组百科全书(KEGG)通路数据库对差异表达的基因进行富集和功能注释。基于STRING数据库及Cytoscape软件构建蛋白质相互作用网络,分析其关键基因簇及网络节点。结果:共纳入3套鼻咽癌基因芯片数据,选出在≥3个数据集中有交集的差异表达基因116个,其中上调基因69个,下调基因47个。差异表达基因GO富集分析发现细胞分裂异常、蛋白结合改变,纺锤体装配异常、细胞外泌体功能改变与鼻咽癌发生发展相关;鼻咽癌组织细胞内部分信号通路发生显著改变,包括DNA修复、细胞外基质受体相互作用、细胞周期、小细胞肺癌、人T细胞白血病病毒1感染等。蛋白质相互作用网络提示存在3个重要的基因簇及4个关键基因。结论:利用生物信息学方法能有效筛选目标基因和信号通路,为鼻咽癌的治疗提供新的策略。

Objective:To screen the key genes of nasopharyngeal carcinoma(NPC)and to explore the pathogenesis of nasopharyngeal carcinoma.Methods:The differentially expressed genes(DEGs)in NPC were identified by Gene Expression Omnibus(GEO)combined with R language.Gene ontology(GO)database and Kyoto Encyclopedia of Genes and Genomes(KEGG)were used for enrichment and functional annotation of DEGs.A protein-protein interaction(PPI)network was constructed based on STRING database and the key gene clusters and network nodes of NPC were further analyzed by Cytoscape software.Results:A total of 3 sets of nasopharyngeal cancer gene chip data were included.116 differentially expressed genes with intersection in this 3 data sets were selected,including 69 up-regulated genes and 47 down-regulated genes.GO enrichment analysis of differentially expressed genes revealed abnormal cell division and spindle assembly,changes in protein biding and in extracellular body function,which were associated with the occurrence and development of nasopharyngeal carcinoma.Some intracellular signaling pathways of nasopharyngeal carcinoma were significantly altered,including DNA repair,extracellular matrix receptor interaction,cell cycle small cell lung cancer,human T-cell leukemia virus 1 infection,etc.The protein interaction network suggests that there are three important gene clusters and four key genes.Conclusion:Bioinformatics can effectively screen target genes and signal pathways,which provides new ideas for the treatment of nasopharyngeal carcinoma.