基于生物信息学分析探索神经母细胞瘤相关的新生物标志物

Analysis and exploration of new biomarkers related to neuroblastoma via bioinformatics

目的利用综合生物信息学分析方法探索神经母细胞瘤(Neuroblastoma,NB)相关的新生物标志物。方法采用GEO2R分别筛选GEO(Gene expression omnibus)数据库GSE39262和GSE66586数据集中NB细胞与对照细胞之间的差异表达基因(Differentially expressed genes,DEGs),利用韦恩图将两组DEGs取交集,利用仙桃学术在线生信分析工具对其进行GO功能富集分析和KEGG通路富集分析,同时利用String数据库绘制蛋白互作网络(Protein-protein interaction,PPI)图,并通过Cytoscape软件中的CytoHubba插件筛选Hub基因。最后使用R2基因组分析和可视化平台(R2 Genomics Analysis and Visualization Platform)整理的NB组织转录组数据对Hub基因进行筛选验证。结果本研究从GSE39262数据集中共筛出845个DEGs,从GSE66586数据集中共筛出2980个DEGs,韦恩图分析出392个共有DEGs。GO/KEGG分析提示,上述共有DEGs主要参与姐妹染色单体分离、DNA复制起始前复合物、单链DNA解旋酶活性、细胞周期、DNA复制和ECM受体相互作用等。从PPI网络中筛出10个核心基因CCNB1、CDC6、KIF2C、BUB1B、CDC20、KIF20A、CCNA2、TOP2A、CDK1和RRM2。10个Hub基因的验证结果显示,BUB1B、CCNB1、CDK1和KIF2C与NB患者的预后及COG风险分级密切相关。结论BUB1B、CCNB1、CDK1和KIF2C在高风险NB组织中高表达,且与患者的预后相关,可能会成为未来研究NB的潜在生物标志物。

Objective To explore new biomarkers related to neuroblastoma through comprehensive bioinformatics.Methods GEO2R was used to identify differentially expressed genes(DEGs)between NB cells and control cells which from GSE39262 and GSE66586 data sets in GEO(Gene expression omnibus)database respectively.Wayne diagram was used to display the common DEGs.Xiantao academic was used to carry out GO function enrichment and KEGG pathway enrichment analysis.String database was used to construct protein-protein interaction network(PPI),and then the Hub genes were screened by CytoHubba plug-in in Cytoscape software.Finally,Hub genes were screened and verified using the NB tissue transcriptome data compiled by R2 Genomics Analysis and Visualization Platform.Results In this study,a total of 845 DEGs were screened from the GSE39262 data set,a total of 2980 DEGs were screened from the GSE66586 data set,and a total of 392 common DEGs were identified by Wayne diagram.GO and KEGG analysis results showed that the above common DEGs were mainly involved in sister chromatid separation,DNA replication preinitiation complex,single-stranded DNA helicase activity,cell cycle,DNA replication and ECM receptor interaction.The top ten Hub genes,namely CCNB1,CDC6,KIF2C,BUB1B,CDC20,KIF20A,CCNA2,TOP2A,CDK1 and RRM2,were screened from the PPI network.The verification results of 10 Hub genes revealed that BUB1B,CCNB1,CDK1 and KIF2C were closely related to the prognosis and COG risk classification of patients with neuroblastoma.Conclusion BUB1B,CCNB1,CDK1 and KIF2C are highly expressed in high risk NB tissues and associated with the prognosis of NB patients,which may serve as potential biomarkers of NB for future research.