生物信息学分析筛选肺腺癌关键基因及通路  

Identification of key genes and pathways of lung adenocarcinoma by bioinformatics analysis

作　　者：余东虎 黄静宇[1] 沈小艳 汪育锦 李胜[2,3] 胡卫东 YU Donghu;HUANG Jingyu;SHEN Xiaoyan;WANG Yujin;LI Sheng;HU Weidong(Department of Cardiothoracic Surgery,Zhongnan Hospital of Wuhan University,Wuhan Hubei 430071,China;Biobank of Zhongnan Hospital of Wuhan University,Wuhan Hubei 430071,China;Human Genetic Resources Preservation Center of Hubei Province,Wuhan Hubei 430071,China)

机构地区：[1]武汉大学中南医院胸心血管外科,湖北武汉430071 [2]武汉大学中南医院生物样本库,湖北武汉430071 [3]湖北省人类遗传资源保藏中心,湖北武汉430071

出　　处：《转化医学杂志》2019年第6期329-332,共4页Translational Medicine Journal

基　　金：湖北省卫生计生委重点支撑项目(WJ2017Z006);武汉大学中南医院科技创新培育基金(CXPY2017041);武汉大学珞珈青年学者科研基金(351人才计划)

摘　　要：目的利用生物信息学分析方法对基因芯片数据进行分析,筛选出肺腺癌相关靶基因并进行验证。方法从美国国立生物技术信息中心创建并维护的基因表达数据库(Gene Expression Omnibus,GEO)中下载编号为GSE10072的基因芯片,得到49例正常肺组织样本和58例肺腺癌组织样本,应用R软件读取原始数据并进行预处理,分析差异表达基因(differentially expressed genes,DEGs),接着对这些DEGs进行聚类分析和功能富集分析,构建蛋白质互作网络,进一步从网络中筛选出核心基因,最后从转录水平和预后来验证分析结果。结果肺腺癌组织和正常肺组织DEGs共888个,其中上调基因有317个,下调基因有571个。根据功能富集分析,细胞粘附、药物反应以及细胞外基质的组成是其较突出的生物学功能,细胞外基质受体相互作用通路以及补体和凝血级联反应通路是其突出的信号通路。得到8个核心基因进一步验证发现,GAPDH,TOP2A,BIRC5和CCNB14个基因的表达量与肺腺癌患者的预后相关。结论筛选出的核心基因可能在肺腺癌发展中具有重要作用,并有可能成为肺腺癌的治疗靶点和诊断靶标。Objective To analyze the microarray data to identify and validate target genes related to lung adenocarcinoma(LUAD).Methods A microarray dataset containing a total of 49 normal pulmonary samples and 58 LUAD samples were obtained from Gene Expression Omnibus(GEO)database.The original data was preprocessed and differentially expressed genes(DEGs)identified with R.Subsequent clustering and functional enrichment were performed.Based on the list of DEGs,a protein-protein interaction network was constructed to locate hub genes.Finally,the significance of the identified key genes was subjected to independent external validation with survival analysis.Results A total of 888 DEGs including 317 up-regulated and 571 down-regulated genes between LUAD and normal pulmonary tissues were identified.According to functional enrichment,cell adhesion,signal transduction and cell adhesion were among the top enriched biological processes ontology and ECM-receptor interaction and complement and coagulation cascades among the top pathways.External validation indicated that all 8 identified hub genes were differentially expressed between LUAD and control group,and GAPDH,TOP2A,BIRC5,CCNB1 were significantly associated with prognosis of LUAD.Conclusion Our study suggests that these hub genes may play important roles in the development of LUAD and may serve as new therapeutic targets and diagnostic targets of LUAD.

关 键 词：肺腺癌 生物信息学 基因芯片 差异表达基因 诊断靶标 

分 类 号：R734.2[医药卫生—肿瘤]