低级别胶质瘤差异基因筛选及功能预测  

Screening and functional prediction of differential genes in low-grade gliomas

作　　者：阿衣希塔·奴尔江 魏珍 刘正 努尔艾合买提·牙力昆 杜鹏[1] Ayishita Nurjiang;Wei Zhen;Liu Zheng Nur Ahmat Yalikun;Du Peng(Neurosurgery department,the second affiliated hospital of Xinjiang Medical University,Urumuqi,Xinjiang,830063,China)

机构地区：[1]新疆医科大学第二附属医院神经外科,新疆乌鲁木齐830063

出　　处：《齐齐哈尔医学院学报》2023年第17期1615-1621,共7页Journal of Qiqihar Medical University

基　　金：新疆维吾尔自治区自然科学基金面上项目(2022D01C273)。

摘　　要：目的 基于美国癌症肿瘤基因图谱(TCGA)数据库联合GTEx数据库分析低级别胶质瘤组织及正常脑组织的差异表达基因,并探讨其相关分子机制。方法 从TCGA数据库及GTEx数据库下载所有低级别胶质瘤中mRNA转录组数据。共包含样本569例,其中低级别胶质瘤组织为529例,正常脑组织为40例。在R语言环境下,应用edge R工具包处理数据,得到差异表达基因。利用DAVID数据库对差异表达的前1000个基因进行GO分析及KEGG通路富集分析。对显著差异表达的前200个差异表达基因进行分析,基于Cysctoscape绘制蛋白互作网络图。比较关键基因在低级别胶质瘤组织及正常脑组织中的表达水平。以关键基因的中位表达水平为界值,将关键基因分为高表达组与低表达组,比较高表达组与低表达组的生存情况。结果 共筛选出9045个差异表达基因,其中,上调基因5566个,下调基因3479个。GO分析结果显示,其生物过程有DNA结合转录激活活性,RNA聚合酶Ⅱ特异性,肌动蛋白结合,有机酸结合,肽结合等功能富集。KEGG富集分析结果表明,差异表达基因的信号通路主要化学致癌物-活性氧自由基,粘附蛋白激酶,肺癌蛋白多糖,催产素通路等信号通路。筛选出节点排在前23位关键基因分别为ASPM、AURKB、KIF11、KIF20A、TOP2A、BUB1、DLGAP5、CCNB2、TTK、CENPF、MKI67、NDC80、BIRC5、CEP55、NCAPG、RRM2、CENPE、TPX2、MELK、ESPL1、HJURP、KIF4A、PBK。进一步分析显示,低级别胶质瘤组织中ASPM、AURKB表达均高于正常脑组织(P<0.05)。从生存分析曲线可知,ASPM和AURKB高表达组总生存时间与低表达组比较,差异有统计学意义(P<0.05)。结论 基于TCGA联合GTEx数据库分析出ASPM与AURKB在低级别胶质瘤中高表达,参与至低级别胶质瘤的增殖,迁移,侵袭,抗凋亡,耐药中,有望成为新的药物靶点及肿瘤标志物。Objective To analyze the differentially expressed genes in low-grade gliomas tissues and normal brain tissues based on The Cancer Genome Atlas(TCGA)database and Genotype-Tissue Expression(GTEx)database,and to explore their related molecular mechanisms.Methods The mRNA transcriptome data of all low-grade gliomas were downloaded from TCGA database and GTEX database.A total of 569 samples were included,among them 529 cases of low-grade glioma and 40 cases of normal brain tissue.In the R language environment,the edge R toolkit was used to process the data to obtain differentially expressed genes.GO analysis and KEGG pathway enrichment analysis of the top 1,000 differentially expressed genes were performed using the DAVID database.Analysis of the top 200 differentially expressed genes that were significantly differentially expressed was performed,and the protein interaction network map was drawn based on Cysctoscape.The expression levels of key genes in low-grade glioma tissues and normal brain tissues were compared.Critical genes were divided into high expression group and low expression group using the median expression level of critical genes as the cut-off value,and the survival of high expression group and low expression group was compared.Results A total of 9045 differentially expressed genes were screened,including 5566 up-regulated genes and 3479 down-regulated genes.GO analysis showed that the differentially expressed genes performed function enriching in DNA binding transcriptional activation activity,RNA polymerase II specificity,actin binding,organic acid binding,peptide binding and other functions in the biological process.The results of KEGG enrichment analysis showed that the signaling pathways of differentially expressed genes were mainly chemical carcinogen-reactive oxygen species,adhesion protein kinase,lung cancer proteoglycan,oxytocin pathway and other signaling pathways.The top 23 key genes were ASPM,AURKB,KIF11,KIF20A,TOP2A,BUB1,DLGAP5,CCNB2,TTK,CENPF,MKI67,NDC80,BIRC5,CEP55,NCAPG,RRM2,CENPE,TPX2

关 键 词：低级别胶质瘤 关键基因 信号通路 

分 类 号：R651.1[医药卫生—外科学]