动脉瘤性蛛网膜下腔出血后迟发性脑缺血的转录组学分析

Transcriptomic analysis of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

目的:基于基因表达数据库(GEO)运用生物信息学的方法分析动脉瘤性蛛网膜下腔出血(aSAH)后发生迟发性脑缺血(DCI)患者的差异表达基因及相关功能和通路。方法:从GEO数据库中筛选符合条件的患者mRNA数据集,将数据分为aSAH后发生DCI的患者组和未发生DCI的对照组,利用R软件进行差异表达基因(DEGs)分析、基因本体(GO)富集分析、京都基因与基因组百科全书(KEGG)通路分析以及基因集富集分析(GSEA),寻找关键基因及相关功能通路。结果:鉴定得到140个差异表达基因;KEGG分析显示,有10条差异有显著性的富集信号通路(P<0.05),主要与低氧诱导因子-1(HIF-1)信号通路、谷氨酸能突触、细胞粘附分子、趋化因子信号通路等相关;根据GO功能分析得到显著富集条目26个,涉及生物过程、细胞组分、分子功能3类条目;GSEA分析表明,细胞外基质受体相互作用以及过氧化物酶体两个通路在患者组与对照组之间具有显著的富集差异。结论:aSAH后DCI的发生涉及到COL17A1、RPL11、FCAMR、GNB2L1、HIF1A等多个基因,并可通过血管功能障碍、炎症反应、神经损伤、氧化应激等多种途径影响DCI的发生。

Objective:To analyze the key differentially expressed genes and related pathways in patients with delayed cerebral ischemia(DCI)occurring after aneurysmal subarachnoid hemorrhage(aSAH)based on gene expression omnibus(GEO)database.Methods:Gene datasets meeting the study requirements were screened from the GEO database and divided into a patient group with DCI after aSAH and a control group without DCI,and differentially expressed genes(DEGs)analysis,gene ontology(GO)enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,and gene set enrichment analysis(GSEA)were performed by using R software to find relevant genes and pathways.Results:A total 140 differentially expressed genes were identified.KEGG analysis showed that there were 10 significantly enriched signaling pathways(P<0.05),mainly related to hypoxia-inducible factor-1(HIF-1)signaling pathway,glutamatergic synapses,cell adhesion molecules,and chemokine signaling pathways,etc.Twenty-six significantly enriched entries were obtained according to the functional analysis of GO,which involved entries in three categories,namely,biological processes,cellular components,and molecular functions.GSEA analysis showed that two pathways,extracellular matrix receptor interactions as well as peroxisomes,had significant enrichment differences between the patient group and the control group.Conclusion:The development of DCI after aSAH involves several genes such as COL17A1,RPL11,FCAMR,GNB2L1,HIF1A,and can affect the development of DCI through various pathways such as vascular dysfunction,inflammatory response,neurological injury,and oxidative stress.