特发性肺动脉高压患者外周血单核细胞差异表达基因分析  

Differentially expressed genes in peripheral blood mononuclear cells in patients with idiopathic pulmonary arterial hypertension

作　　者：郭海森 张炜岱 倪楚民[1] 周琳洁 蔡志雄[1] 朱稚丹[1] Guo Haisen;Zhang Weidai;Ni Chumin;Zhou Linjie;Cai Zhixiong;Zhu Zhidan(Department of Cardiology,Shantou Central Hospital,Shantou Hospital Affiliated to Sun Yat-sen University,Shantou 515031,Guangdong,China)

机构地区：[1]汕头市中心医院中山大学附属汕头医院心血管内科,广东汕头515031

出　　处：《广州医科大学学报》2021年第4期33-38,共6页Academic Journal of Guangzhou Medical University

基　　金：广东省医学科学技术研究基金项目(A2019219);汕头市自筹经费计划项目(汕府科[2020]5号-7);广东省科技创新战略专项资金(纵向协同管理方向)(2018-157-42)。

摘　　要：目的:探究特发性肺动脉高压(IPAH)患者的外周血单核细胞差异表达基因及相关信号通路,为进一步研究和临床诊疗提供新的靶点。方法:通过GEO数据库获取GSE33463基因芯片数据集,筛选特发性肺动脉高压(IPAH,30例)作为研究组,分别与对照组(41例)和系统性硬化病相关肺动脉高压组(SSc-PAH,42例)进行比较分析。采用R软件和GEO2R工具筛选差异表达基因,并进行GO基因本体分析、KEGG信号通路分析和蛋白质相互作用分析。结果:与对照组相比,IPAH组外周血单核细胞共筛选33个上调基因和51个下调基因。上调基因中HBD、NFE2、HBE1、HBG1、EPB42、SELENBP1、AHSP、SNCA、ALAS2、HBG2、HBQ1和HBM共12个基因为枢纽基因,主要参与血红蛋白复合体组成、氧转运蛋白活性调节、氧输送、氧结合等生物学过程。下调基因中JUNB、JUN、NFKBIA和FOSB4为枢纽基因,主要参与AP-1转录因子信号传导、对激素刺激反应等生物学过程。与SSc-PAH组相比,IPAH组共筛选出1个上调基因(RBPMS2)和18个下调基因,下调基因中OAS2、OAS3、IFI6和IFITM3作为枢纽基因参与免疫反应过程。结论:IPAH患者外周血单核细胞的红系基因表达上调和AP-1信号传导下调可能在IPAH的发生发展过程中发挥重要作用,可以作为进一步临床研究的方向。OAS2、OAS3、IFI6和IFITM3基因可能有助于IPAH与SSc相关肺动脉高压的鉴别诊断。Objective:To investigate the differentially expressed genes in peripheral blood mononuclear cells and related signal pathways in patients with idiopathic pulmonary arterial hypertension(IPAH),so as to shed light on new targets for further research and clinical management.Methods:From the GSE33463 gene-chip dataset was obtained from GEO database,patients with IPAH were included as the study group(n=30)and compared with a control group(n=41)and a group with systemic sclerosis-related pulmonary arterial hypertension(SSc-PAH,n=42).R software and the online GEO2R tool was to screen differentially expressed genes which were then subjected to gene ontology(GO)analysis,KEGG signaling pathway analysis and protein-protein interaction analysis.Results:Compared with the control group,33 up-regulated and 51 down-regulated genes were screened from the peripheral blood mononuclear cells of the IPAH group.Among the up-regulated,12 genes including HBD,NFE2,HBE1,HBG1,EPB42,SELENBP1,AHSP,SNCA,ALAS2,HBG2,HBQ1 and HBM were hub genes mainly involved in biological process such as composition of hemoglobin complex,regulation of oxygen transporter activity,oxygen delivery and binding.Among the down-regulated,JUNB,JUN,NFKBIA and FOSB4 were hub genes mainly involved in biological processes such as signaling pathway of AP-1 transcription factor and response to hormone stimulation.Compared with the SSc-PAH group,the IPAH group screened out one up-regulated(RBPMS2)and 18 down-regulated genes.Among the down-regulated,OAS2,OAS3,IFI6 and IFITM3 were involved in immune responses.Conclusion:Up-regulation of erythroid gene expression and down-regulation of AP-1 signaling pathway in peripheral blood mononuclear cells of IPAH patients may play an important role in the development and progression of IPAH.These findings may show the direction of further clinical studies.OAS2,OAS3,IFI6 and IFITM3 genes may contribute to the differential diagnosis between IPAH and SSc-related pulmonary arterial hypertension.

关 键 词：肺动脉高压 特发性肺动脉高压 系统性硬化病 单核细胞 生物信息学 

分 类 号：R543.2[医药卫生—心血管疾病]