基于信息学分析的帕金森病额叶基因表达谱研究  

Gene expression profile of frontal lobe in Parkinson disease based on bioinformatics analysis

作　　者：吴欣桐[1] 洪培伟 WU Xintong;HONG Peiwei(Department of Neurology,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,P.R.China;Department of Geriatrics and Neurology,West China School of Public Health and West China Forth Hospital,Sichuan University,Chengdu,Sichuan 610041,P.R.China)

机构地区：[1]四川大学华西医院神经内科,成都610041 [2]四川大学华西公共卫生学院/华西第四医院老年医学/神经内科,成都610041

出　　处：《华西医学》2019年第10期1117-1125,共9页West China Medical Journal

摘　　要：目的采用生物信息学方法分析帕金森病(Parkinson disease,PD)患者额叶组织的基因表达谱,来探索PD抑郁相关的机制。方法从Gene Expression Omnibus(GEO)数据库中使用“Parkinson disease”进行检索,并限定组织来源为人类(Homo sapiens)及检测方法为表达谱芯片(Expression profiling by array),获取2019年3月20日前GEO数据库中的所有生物信息数据。使用ImaGEO(Integrative Gene Expression Meta-Analysis fromGEO database)、DAVID(the Database for Annotation,Visualization and Integrated Discovery)、STRING在线工具及Cytoscape 3.6.1软件进行数据分析。结果根据检索条件,获得了2个数据集,共45个样本(PD组24个,健康对照组21个)。与健康对照组相比,PD组的额叶中总共有236个基因表达存在差异,其中146个基因表达水平增高,90个基因表达水平下降。根据基因本体论分析及京都基因和基因组数据库分析,该差异基因主要富集在突触后膜、细胞膜成分、突触后膜密集区、髓鞘等结构。差异基因参与了和PD发生有关的多巴胺能、谷氨酸能及γ-氨基丁酸能等神经突触的生物过程、抑郁的发生过程和多条信号通路(如:丝裂原激活蛋白激酶信号通路、p53信号通路及Wnt信号通路);其中关键蛋白是NFKBIA、NRXN1和RPL35A。结论PD患者额叶的基因表达与PD抑郁发生有关。该研究为进一步理解PD抑郁的发病机制提供了理论依据。Objective To conduct a bioinformatics analysis of gene expression profiles in frontal lobe of patients with Parkinson disease(PD),in order to explore the potential mechanism related to depression in PD.Methods All the bioinformatics data before March 20th 2019 were acquired from Gene Expression Omnibus(GEO)database,using“Parkinson disease”as the key word.The species was limited to human(Homo sapiens),and the detective method was limited to expression profiling by array.ImgGEO(Integrative Gene Expression Meta-Analysis from GEO database),DAVID(the Database for Annotation,Visualization and Integrated Discovery),STRING and Cytoscape 3.6.1 software were utilized for data analysis.Results Totally,45 samples(24 PD cases and 21 healthy controls)were obtained from 2 datasets.We identified 236 differentially expressed genes(DEGs)in the post-mortem frontal lobe between PD cases and healthy controls,in which 146 genes were up-regulated and 90 genes were down-regulated.Based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis,the DEGs were mainly enriched in the structures of postsynaptic membrane,cell membrane component,postsynaptic membrane dense area,and myelin sheath,and were involved in the occurrence of PD,depression,and other diseases.These genes were involved in the biological processes of dopaminergic,glutamate-nergic,GABA-nergic synapses,and some other synapses,as well as several signaling pathways(e.g.mitogen-activated protein kinase signal pathway,p53 signal pathway,and Wnt signal pathway),which were associated with PD and depression pathogenesis.Besides,we found that NFKBIA,NRXN1,and RPL35A were the Hub proteins.Conclusions Gene expression in frontal lobe of patients with PD is associated with the pathogenesis of PD.This study provides a theoretical basis for understanding the mechanism of PD occurrence and progression,as well as the potential mechanism of depression in PD.

关 键 词：帕金森病 额叶 非运动症状 抑郁 生物信息学 

分 类 号：R742.5[医药卫生—神经病学与精神病学] Q811.4[医药卫生—临床医学]