使用DNA微阵列分析研究系统性血管炎潜在的基因靶点  

Identification of potential gene targets in systemic vasculitis using DNA microarray analysis

作　　者：史卫军 冯怡雯[2] 汤敬东 Shi Weijun;Feng Yiwen;Tang Jingdong(Department of Vascular Surgery, Fudan University Pudong Medical Center, Shanghai 201399, China;Department of General Surgery Center, Shanghai General Hospital, Shanghai 200080, China)

机构地区：[1]上海市浦东医院血管外科,上海201399 [2]上海市第一人民医院普外科中心,上海200080

出　　处：《血管与腔内血管外科杂志》2017年第6期1028-1035,共8页Journal of Vascular and Endovascular Surgery

摘　　要：本研究旨在确定系统性血管炎中关键基因,从而获得新的潜在的基因靶向位点来治疗系统性血管炎。从Gene Expression Omnibus数据库中下载了GSE16945的双色cDNA微阵列数据,由来自13名系统性血管炎患者和16名健康对照组成员的外周单核细胞标本组成。通过BRB Array Tools,在系统性血管炎中筛选差异表达基因(DEG),随后使用cluster Profiler包构建蛋白质-蛋白质相互作用(PPI)网络以及选择显著功能相互作用(FI)模块。此外,预测了确定的DEG之间的转录因子(TF),并构建了转录调控网络。鉴定了总共173个上调基因和93个下调的基因,主要与免疫应答途径相关。FBJ小鼠骨肉瘤病毒基因同源物(FOS),泛素B(UBB),信号转导和转录激活因子1(STAT1)和MX dynamin样GTPase 1(MX1)在PPI网络中被鉴定为中枢蛋白。此外,UBB、FOS和STAT1分别是三个确定的FI模块中的中枢蛋白。在DEGs中总共预测了9个转录因子。在预测为转录因子的DEG中,鉴定了相互作用的STAT1,v-maf禽类肌肉痉挛性纤维肉瘤癌基因同源物B(MAFB)和酪氨酸3-单加氧酶/色氨酸5-单加氧酶活化蛋白Z(YWHAZ),这些转录因子作为靶点进一步调节其他DEGs。包括FOS、UBB、MX1、STAT1、MAFB和YWHAZ在内的各种基因可能是用于治疗系统性血管炎的潜在靶标。The present study aimed to identify the involvement of critical genes in systemic vasculitis, to gain an improved understanding of the molecular circuity and to investigate novel potential gene targets for systemic vasculitis treatment. The dualcolor c DNA microarray data of GSE16945, consisting of peripheral mononuclear blood cell specimens from 13 patients with systemic vasculitis and 16 healthy controls, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes（DEGs） were screened in systemic vasculitis compared with controls using BRB Array Tools, followed by the construction of a proteinprotein interaction（PPI） network using the cluster Profiler package, and significant functional interaction（FI） module selection. Furthermore, transcriptional factors（TFs） among the identified DEGs were predicted and a transcriptional regulation network was constructed. A total of 173 up-and 93 downregulated genes were identified, which were mainly associated with immune response pathways. FBJ murine osteosarcoma viral oncogene homolog（FOS）, ubiquitin B（UBB）, signal transducer and activator of transcription 1（STAT1） and MX dynaminlike GTPase 1（MX1） were identified as hub proteins in the PPI network. Furthermore, UBB, FOS, and STAT1 were hub proteins in the three identified FI modules, respectively. In total, nine TFs were predicted among the DEGs. Of the DEGs that were predicted to be TFs, STAT1, vmaf avian musculoaponeurotic fibrosarcoma oncogene homolog B（MAFB） and tyrosine 3 monooxygenase/tryptophan 5 monooxygenase activation protein Z（YWHAZ）, which interacted with each other, were identified to regulate further DEGs as target genes. Various genes, including FOS, UBB, MX1, STAT1, MAFB, and YWHAZ may be potential targets useful for the treatment of systemic vasculitis.

关 键 词：差异表达基因 蛋白质-蛋白质相互作用网络 功能相互作用 系统性血管炎 

分 类 号：R543[医药卫生—心血管疾病]