特发性与继发性肺动脉高压基因表达差异的生物信息学证据  

Difference on Gene Expression between Idiopathic Pulmonary Arterial Hypertension and Secondary Pulmonary Arterial Hypertension:Evidence from Bioinformatics Analysis

作　　者：王景蓉 于浩滢 任淑月 吕婷婷 孙岚[1] 杜冠华[1] WANG Jing-rong;YU Hao-ying;REN Shu-yue;LV Ting-ting;SUN Lan;DU Guan-hua(Beijing Key Laboratory of Drug Target Research and Drug Screening,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国医学科学院,北京协和医学院,药物研究所,药物筛选研究中心,药物靶点研究和新药筛选北京市重点实验室,北京市100050

出　　处：《中国分子心脏病学杂志》2020年第5期3574-3578,共5页Molecular Cardiology of China

基　　金：国家自然科学基金面上项目(82070056、81670456);重大新药创制科技重大专项(2018ZX09711001-003-011、2018ZX09711001-012)。

摘　　要：目的通过生物信息学方法分析特发性与继发于先天性心脏病的肺动脉高压(pulmonary arterial hypertension,PAH)的差异表达基因(differentially expressed genes,DEGs)。方法从基因表达数据库(gene expression omnibus,GEO)下载PAH患者的肺组织芯片数据集,其中包括特发性肺动脉高压(idiopathic pulmonary arterial hypertension,IPAH)患者,继发于先天性心脏病的肺动脉高压(pulmonary arterial hypertension secondary to congenital heart disease,CHD-PAH)患者及正常肺组织的基因表达数据。通过GEO2R在线分析鉴定IPAH与CHD-PAH的DEGs,得到二者的共同差异基因。使用DAVID数据库(the database for annotation,visualization and integrated discovery)对DEGs进行功能和通路富集分析。运用STRING数据库(search tool for the retrieval of interacting genes)及Cytoscape软件对DEGs进行蛋白相互作用网络(protein-protein interaction,PPI)分析。结果在IPAH及CHD-PAH中分别鉴定出515与613个DEGs。二者包含357个共同差异基因,但其在IPAH与CHD-PAH中具有相反的表达趋势。功能与通路富集结果表明共同差异基因主要参与细胞增殖、RNA及核糖体相关的生物过程。IPAH与CHD-PAH中DEGs的PPI网络及关键基因也已分析并筛选。结论本研究对IPAH与CHD-PAH基因表达差异的探索有利于进一步研究二者病理机制及分子水平上的差异,寻找关键靶点,更精准地制定相应的治疗策略。Objective To explore the difference between idiopathic pulmonary arterial hypertension(IPAH)and PAH secondary to congenital heart disease(CHD-PAH)at genomic level by bioinformatics analysis.Methods Microarray datasets GSE113439 was downloaded from Gene Expression Omnibus(GEO)database,which included the gene data of lung tissues from IPAH patients,(CHDPAH)patients and normal tissues.The differentially expressed genes(DEGs)in each PAH were identified by GEO2 R,and the common differential genes were obtained.Functional and pathway enrichment analysis were performed using the Database for Annotation,Visualization and Integrated Discovery(DAVID).Search Tool for the Retrieval of Interacting Genes(STRING)and Cytoscape were utilized for protein-protein interaction(PPI)networks.Results There were 515 DEGs in IPAH and 613 DEGs in CHD-PAH identified,respectively.Totally 357 common differential genes were obtained,which had the opposite expressions between IPAH and CHD-PAH.The enrichments of function and pathway mainly included cell proliferation,RNA and ribosome relative processing.The PPI networks of DEGs in each PAH were analyzed,and the top ten genes were calculated successfully.Conclusion The exploration of differences on gene expression between IPAH and CHD-PAH is beneficial to further studies on pathological mechanism and their differences on molecular level,as well as finding therapeutic targets and making precise treatment strategies.

关 键 词：生物信息学 差异表达基因 特发性肺动脉高压 继发性肺动脉高压 先天性心脏病 

分 类 号：R544.1[医药卫生—心血管疾病] Q811.4[医药卫生—内科学]