基于生物信息学筛选、分析和验证骨肉瘤差异基因  

Screening,Analysis and Validation of Differentially Expressed Genes in Osteosarcoma Based on Bioinformatics

作　　者：郭良煜 余铃[1] 陈敬腾 龚长天 施玉博 郭卫春[1] Guo Liangyu;Yu Ling;Chen Jingteng;Gong Changtian;Shi Yubo;Guo Weichun(Department of Orthopedics,Renmin Hospital of Wuhan University,Wuhan 430060,Hubei,China)

机构地区：[1]武汉大学人民医院骨科,武汉430060

出　　处：《肿瘤预防与治疗》2021年第3期228-233,共6页Journal of Cancer Control And Treatment

基　　金：国家自然科学基金(编号:81341078)。

摘　　要：目的:采用生物信息学的方法筛选出骨肉瘤差异基因,并探讨其与骨肉瘤发生的关系.方法:从GEO数据库中下载符合标准的数据集,用GEO2R进行差异分析,随后用DAVID进行Gene Ontology(GO)富集分析和Kyoto En-cyclopedia of Genes and Genomes通路分析,随后利用STRING数据库和Cytoscape软件做蛋白相互作用图,用插件Cy-tohubb以Degree为标准筛选差异基因,最后将得到的基因用HCMDB数据库进行验证.结果:从GSE36001和GSE12865中共筛选出421个差异基因,其中有187个基因是上调基因,234个基因是下调基因.GO分析的结果显示在生物进程方面,差异基因参与的生物学过程有激活蛋白激酶活性和正性调控肽基酪氨酸磷酸化;分子功能方面,差异基因的功能有调控蛋白的结合和肝素结合;细胞成分方面,差异基因存在于胞外外泌体和突触前膜中;信号通路方面,差异基因参与了Rap1信号通路的调控.此外,用Cytohubb筛选出排名前5的基因:SMAD2、CD44、CX-CL12、UBE2D3和KEAP1.最终用HCMDB数据库进行验证,发现CD44、CXCL12、UBE2D3和KEAP1在骨肉瘤中均下调.结论:在骨肉瘤中下调的CD44、CXCL12、UBE2 D3和KEAP1可能与骨肉瘤的发生发展有关.Objective: To screen out the differentially expressed genes(DEGs) in osteosarcoma by bioinformatics and discuss their relation to osteosarcoma. Methods: Standardized datasets were downloaded from GEO database;DEGs were analyzed with GEO2 R(an interactive web tool);Gene Ontology(GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted by DAVID database;protein-protein interaction network diagram was drawn with STRING database and Cytoscape software;the Degree method provided by Cytohubb(a Cytoscape plugin) was used to screen DEGs;and HCMDB database was used to verify those target genes. Results: A total of 421 DEGs were screened from GSE36001 and GSE12865 databases. 187 genes were up-regulated and 234 genes are down-regulated. The results of GO analysis showed that DEGs mainly existed in extracellular exosomes and presynaptic membranes;they regulated the activation of protein kinase activity, protein and heparin binding as well as Ras1 signaling pathway;and positively regulated peptide tyrosine phosphorylation. In addition, five hub genes(SMAD2, CD44, CXCL12, UBE2 D3 and KEAP1) were selected by using Cytohubb. And we finally verified that CD44, CXCL12, UBE2 D3 and KEAP1 were down-regulated in osteosarcoma verified by using the HCMDB database. Conclusion: Down-regulated CD44, CXCL12, UBE2 D3 and KEAP1 may be related to the pathogenesis and clinical treatment of osteosarcoma.

关 键 词：骨肉瘤 生物信息学 基因 差异表达 

分 类 号：R738.1[医药卫生—肿瘤]