生物信息学分析鉴定出高安动脉炎患者外周血单个核细胞中三个潜在的关键差异表达基因。

Bioinformatic Analysis Identifies Three Potentially Key Differentially Expressed Genes in Peripheral Blood Mononuclear Cells of Patients with Takayasu's Arteritis.

作者信息

Huang Renping, He Yang, Sun Bei, Liu Bing

机构信息

Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

Department of Anesthesiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

Cell J. 2018 Jan;19(4):647-653. doi: 10.22074/cellj.2018.4991. Epub 2017 Nov 4.

DOI:10.22074/cellj.2018.4991

PMID:29105401

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5672105/

Abstract

OBJECTIVES

This study aimed to identify several potentially key genes associated with the pathogenesis of Takayasu's arteritis (TA). This identification may lead to a deeper mechanistic understanding of TA etiology and pave the way for potential therapeutic approaches.

MATERIALS AND METHODS

In this experimental study, the microarray dataset GSE33910, which includes expression data for peripheral blood mononuclear cell (PBMC) samples isolated from TA patients and normal volunteers, was downloaded from the publicly accessible Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified in PBMCs of TA patients compared with normal controls. Gene ontology (GO) enrichment analysis of DEGs and analysis of protein-protein interaction (PPI) network were carried out. Several hub proteins were extracted from the PPI network based on node degrees and random walk algorithm. Additionally, transcription factors (TFs) were predicted and the corresponding regulatory network was constructed.

RESULTS

A total of 932 DEGs (372 up- and 560 down-regulated genes) were identified in PBMCs from TA patients. Interestingly, up-regulated and down-regulated genes were involved in different GO terms and pathways. A PPI network of proteins encoded by DEGs was constructed and RHOA, FOS, EGR1, and GNB1 were considered to be hub proteins with both higher random walk score and node degree. A total of 13 TFs were predicted to be differentially expressed. A total of 49 DEGs had been reported to be associated with TA in the Comparative Toxicogenomics Database (CTD). The only TA marker gene in the CTD database was NOS2, confirmed by three studies. However, NOS2 was not significantly altered in the analyzed microarray dataset. Nevertheless, NOS3 was a significantly down-regulated gene and was involved in the platelet activation pathway.

CONCLUSIONS

RHOA, FOS, and EGR1 are potential candidate genes for the diagnosis and therapy of TA.

摘要

目的

本研究旨在鉴定几个与大动脉炎（TA）发病机制相关的潜在关键基因。这一鉴定可能有助于更深入地理解TA的病因机制，并为潜在的治疗方法铺平道路。

材料与方法

在本实验研究中，从可公开访问的基因表达综合数据库（GEO）下载了微阵列数据集GSE33910，该数据集包含从TA患者和正常志愿者中分离的外周血单核细胞（PBMC）样本的表达数据。与正常对照相比，鉴定TA患者PBMC中的差异表达基因（DEG）。对DEG进行基因本体（GO）富集分析和蛋白质-蛋白质相互作用（PPI）网络分析。基于节点度和随机游走算法从PPI网络中提取几个枢纽蛋白。此外，预测转录因子（TF）并构建相应的调控网络。

结果

在TA患者的PBMC中总共鉴定出932个DEG（372个上调基因和560个下调基因）。有趣的是，上调和下调基因涉及不同的GO术语和途径。构建了由DEG编码的蛋白质的PPI网络，RHOA、FOS、EGR1和GNB1被认为是具有较高随机游走分数和节点度的枢纽蛋白。总共预测有13个TF差异表达。在比较毒理基因组学数据库（CTD）中，共有49个DEG被报道与TA相关。CTD数据库中唯一的TA标记基因是NOS2，有三项研究证实。然而，在分析的微阵列数据集中，NOS2没有显著变化。尽管如此，NOS3是一个显著下调的基因，并且参与血小板激活途径。