综合生物信息学对胶质瘤替莫唑胺耐药的中枢基因的鉴定研究

Identification of hub genes for temozolomide resistance in glioma by integrated bioinformatics

目的通过综合生物信息学方法分析并鉴定出胶质瘤替莫唑胺耐药的中枢基因,为胶质瘤耐药机制研究和临床治疗提供新的方向。方法R语言筛选差异表达基因(DEGs);基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析其功能及通路;蛋白质-蛋白质相互作用(PPI)分析筛选DEGs的中枢基因(hub genes);Gliovis数据库验证原发与复发胶质瘤组织中hub genes的mRNA表达及对其进行生存分析。结果共筛选1230个DEGs,其中648个上调基因及582个下调基因。GO显示DEGs在生物过程(BP)上参与核糖体的生物发生、核糖核蛋白复合体生物合成、rRNA加工等;细胞组分(CC)包括线粒体基质、浓缩染色体、染色体区域等;在分子功能(MF)上参与催化活性,作用于RNA、转移酶活性等。KEGG显示DEGs主要参与核质转运、细胞周期、DNA复制等。PPI筛选出TOP10中枢基因:BUB1B、ASPM、KIF4A、CDC6、NCAPG、MCM7、MCM3、MCM5、MCM10、RFC4;Gliovis数据库分析显示BUB1B、ASPM、KIF4A、CDC6、NCAPG、MCM3、MCM5、MCM10、RFC4在复发胶质瘤组织中表达相对上调而且与生存期呈负相关。结论通过综合生物信息学分析并鉴定出在耐药胶质瘤细胞和复发胶质瘤组织中高表达且与生存期呈负相关的BUB1B、ASPM、KIF4A、CDC6、NCAPG、MCM3、MCM5、MCM10、RFC4作为胶质瘤替莫唑胺耐药的中枢基因。

Objective To analyze and identify hub genes of temozolomide resistance in glioma by an integrated bioinformatics approach,and to provide new directions for the study of drug resistance mechanisms and clinical treatment of glioma.Methods R-language was used to screen for differentially expressed genes(DEGs).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis was used to analyze their functions and pathways.Protein-protein interaction(PPI)analysis was used to screen for hub genes.The Gliovis database was used to verify the mRNA expression of hub genes in primary and recurrent glioma tissues and to analyze their survival.Results A total of 1230 DEGs were screened,including 648 up-regulated genes and 582 down-regulated genes.GO showed that DEGs were involved in ribosome biogenesis,ribonucleoprotein complex biosynthesis and rRNA processing in terms of biological processes(BP).Cellular components(CC)included mitochondrial matrix,condensed chromosomes,chromosomal regions,etc.In terms of molecular functions(MF),DEGs participated in catalytic activity,acting on RNA,transferase activity,etc.KEGG showed that DEGs were mainly involved in nucleoplasmic transport,cell cycle,DNA replication,etc.PPI screened TOP10 hub genes:BUB1B,ASPM,KIF4A,CDC6,NCAPG,MCM7,MCM3,MCM5,MCM10,RFC4.Analysis of the Gliovis database showed that BUB1B,ASPM,KIF4A,CDC6,NCAPG,MCM3,MCM5,MCM10 and RFC4 were relatively up-regulated in recurrent glioma tissues and negatively correlated with survival.Conclusion BUB1B,ASPM,KIF4A,CDC6,NCAPG,MCM3,MCM5,MCM10 and RFC4,which are highly expressed in drug-resistant glioma cells and recurrent glioma tissues and negatively correlated with survival,are identified as hub genes for temozolomide resistance in glioma by comprehensive bioinformatics analysis.