生物信息学分析干扰素信号通路在神经母细胞瘤远处转移中的作用

Identification of interferon signaling pathway in distant metastasis of neuroblastoma via bioinformatics analysis

目的:通过生物信息学分析,确定神经母细胞瘤转移相关的枢纽基因,并探究其在转移与预后中发挥的作用。方法:从GEO数据库下载包含神经母细胞瘤原发灶与转移灶的基因芯片原始数据,筛选差异表达基因并进行GO与KEGG富集分析,在STRING数据库中构建蛋白质互作用网络,在Cytoscape中筛选枢纽基因,并通过外部数据集进行验证。此外,在R2平台上对枢纽基因进行生存分析。构建加权基因共表达网络筛选转移相关的模块。结果:共有320个差异表达基因,其中上调162个,下调158个。10个枢纽基因分别是IFI44L、IFI44、HERC5、HERC6、USP18、DDX60、ISG15、RSAD2、MX1、MX2。干扰素信号通路相关基因在转移性神经母细胞瘤中表达差异显著。结论:生物信息学分析为神经母细胞瘤转移的机制提供了新的视角。干扰素信号通路相关基因有望成为诊断标志物及治疗靶点。

Objective:Using bioinformatics analysis to identify hub genes associated with neuroblastoma metastasis and explore their roles in metastasis and prognosis.Methods:Microarray data of neuroblastoma was downloaded from GEO database,including samples from localized site and metastatic site.Differentially expressed genes were screened and functional enrichment analyses of differentially expressed genes including GO and KEGG was conducted.Protein-protein interaction network was constructed in STRING database.Hub genes were identified in Cytoscape software.Furthermore,we performed the survival analysis of hub genes in R2 platform.Weighted gene co-expression network analysis was conducted to identify the co-expression network of differentially expressed genes.Results:A total of 320 differentially expressed genes of which 162 were upregulated and 158 were down-regulated were screened.10 hub genes were identified,which were IFI44L,IFI44,HERC5,HERC6,USP18,DDX60,ISG15,MX1,RSAD2 and MX2.IFN signature was significant differentially expressed in metastatic neuroblastoma.Conclusion:Our study brings a new perspective to understand the metastasis of neuroblastoma.Collectively,we suggested that IFN signature may be potential prognostic markers and therapeutic biomarkers for neuroblastoma.