加权基因共表达网络分析鉴定干燥综合征关键基因及通路-现代医学

加权基因共表达网络分析鉴定干燥综合征关键基因及通路

单位：1. 苏州大学附属第一医院风湿科, 江苏苏州 215006;
2. 苏州大学附属独墅湖医院信息科, 江苏苏州 215006

分类号：R593

出版年·卷·期（页码）：2023·51·第九期（1246-1251）

摘要：

目的：通过生物信息学方法探索干燥综合征(SS)关键基因及通路。方法： 从GEO数据库下载SS患者基因芯片数据，通过加权基因共表达网络分析(WGCNA)，筛选出与临床信息相关性最高的核心模块，将核心模块内基因导入STRING数据库构建蛋白互作网络，并采用Cytoscape软件筛选出核心基因并在GeneMANIA中进行功能分析及验证。结果：通过WGCNA共筛选出14个模块，其中MEyellow模块与临床相关性最高作为核心模块。采用Cytoscape软件筛选出连接度最高的前5位基因IFIT1、IFIT3、MX1、RSAD2、XAF1作为关键基因，GeneMANIA功能分析显示5个关键基因及其相关联基因主要参与Ⅰ型干扰素信号通路、病毒应答通路。在数据集GSE51092中，关键基因IFIT1、IFIT3、MX1、RSAD2、XAF1表达水平均明显高于健康对照组(P＜0.01)，且受试者工作特征(ROC)曲线表明，关键基因IFIT1、IFIT3、RSAD2、XAF1均可区分SS患者与健康人群[均曲线下面积(AUC)＞0.85，P＜0.01]。结论：通过生物信息学分析鉴定IFIT1、IFIT3、MX1、RSAD2、XAF1可能是与SS相关的关键基因，为探究SS的发病机制提供了理论依据与新的方向。

Objective: To identify the key genes and functionally enriched pathways of sjgren's syndrome(SS)by bioinformatics analysis.Methods: We downloaded the microarray datas of SS from Gene Expression Omnibus(GEO).Gene network was constructed and genes were classified into different modules using the weighted gene co-expression network analysis(WGCNA). Function enrichment analysis of the hub module most associated with SS was performed. The genes in the hub module were imported into the STRING database,the protein-protein interaction network was constructed,then the hub genes were screened by Cytoscape software,verified and analyzed function by GeneMANIA.Results: Genes were classified into 14 modules using WGCNA.Among them,the ME yellow module was most closely associated with SS.The top five hub genes with the highest connectivity were IFIT1,IFIT3,MX1,RSAD2 and XAF1 screened by Cytoscape software.These genes were significantly enriched in regulation of type I interferon production and response to virus.The expression levels of the five key genes were confirmed in dataset GSE51092.Receiver operating characteristic(ROC) curve analysis determined that IFIT1,IFIT3,RSAD2,XAF1expression can distinguish SS from controls with all area under curve(AUC) more than 0.85,P＜0.01. Conclusion: Bioinformatics analysis shows that IFIT1, IFIT3, MX1, RSAD2, XAF1 may be the pivot genes related to SS，which provides a theoretical basis and a new direction for the pathogenesis research of SS.

参考文献：

[1] QIN B D,WANG J Q,YANG Z X,et al.Epidemiology of primary sjögren's syndrome:a systematic review and meta-analysis[J].Ann Rheum Dis,2015,74(11):1983-1989.
[2] MARIETTE X,CRISWELL L A.Primary sjögren's syndrome[J].N Engl J Med,2018,378(10):931-939.
[3] NOCTURNE G,MARIETTE X.Advances in understanding the pathogenesis of primary sjogren's syndrome[J].Nat Rev Rheumatol,2013,9(9):544-556.
[4] 高雅静,庞春艳,王永福.干燥综合征相关自身抗体检测的研究进展[J].东南大学学报(医学版),2021,40(5):704-707.
[5] SHIBOSKI C H,SHIBOSKI S C,SEROR R,et al.2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary sjögren's syndrome:a consensus and data-driven methodology involving three international patient cohorts[J].Ann Rheum Dis,2017,76(1):9-16.
[6] THEANDER E,JONSSON R,SJÖSTRÖM B,et al.Prediction of sjögren's syndrome years before diagnosis and identification of patients with early onset and severe disease course by autoantibody profiling[J].Arthritis Rheumatol,2015,67(9):2427-2436.
[7] LANGFELDER P,HORVATH S.WGCNA:an R package for weighted correlation network analysis[J].BMC Bioinformatics,2008,29(9):559-570.
[8] JAMES K,AL-ALI S,TARN J,et al.A transcriptional signature of fatigue derived from patients with primary sjögren's syndrome[J].PLoS One,2015,10(12):e0143970.
[9] TASAKI S,SUZUKI K,NISHIKAWA A,et al.Multiomic disease signatures converge to cytotoxic CD8 T cells in primary Sjögren's syndrome[J].Ann Rheum Dis 2017,76(8):1458-1466.
[10] LESSARD C J,LI H,ADRIANTO I,et al.Variants at multiple loci implicated in both innate and adaptive immune responses are associated with sjögren's syndrome[J] Nat Genet,2013,45(11):1284-1292.
[11] CLOUGH E,BARRETT T.The gene expression omnibus database[J].Methods Mol Biol,2016,1418:93-110.
[12] 饶钰君,田龙龙,张勇斌,等.pSS患者外周血和唇腺组织中差异表达基因生物学功能分析、关键基因筛选及唇腺组织中免疫细胞变化观察[J].山东医药,2022,62(21):48-53.
[13] 赵文甲,刘维,吴沅皞.干燥综合征相关差异表达基因的筛选[J].医学研究生学报,2018,31(9):916-920.
[14] VIVINO F B,BUNYA V Y,GIACOMINA M G,et al.Sjogren's syndrome:an update on disease pathogenesis,clinical manifestations and treatment[J].Clin Immunol,2019,203:81-121.
[15] JAMES J A,HARLEY J B,SCOFIELD R H.Role of viruses in systemic lupus erythematosus and Sjogren syndrome[J].Curr Opin Rheumatol,2001,13(5):370-376.
[16] 李华,王吉波,王丽琴.干燥综合征患者EB病毒感染分析[J].中华医院感染学杂志,2014,24(24):6154-6155,6176.
[17] YAO Y,LIU Z,JALLAL B,et al.Type I interferons in sjogren's syndrome[J].Autoimmun Re,2013,12(5):558-566.
[18] BRKIC Z,MARIA N I,HELDEN-MEEUWSEN C G,et al.Prevalence of interferon type I signature in CD14 monocytes of patients with sjogren's syndrome and association with disease activity and BAFF gene expression[J].Ann Rheum Dis,2013,72(5):728-735.
[19] ZHU H,ZHENG J,ZHOU Y,et al.Knock down of RSAD2 attenuates B cell hyperactivity in patients with primary sjögren's syndrome(pSS) via suppressing NF-κb signaling pathway[J].Mol Cell Biochem,2021,476(5):2029-2037.
[20] LIU B Q,LIU R B,LI W P,et al.XAF1 prevents hyperproduction of type I interferon upon viral infection by targeting IRF7[J].EMBORep,2023,24(1):e55387.
[21] MARIA N I,BRKIC Z,WARIS M,et al.MXA as a clinically applicable biomarker for identifying systemic interferon type I in primary sjogren's syndrome[J].Ann Rheum Dis,2014,73(6):1052-1059.
[22] MARIA N I,STEENWIJK E C,IJPMA A S,et al.Contrasting expression pattern of RNA-sensing receptors TLR7,RIG-I and MDA5 in interferon-positive and interferon-negative patients with primary sjögren's syndrome[J].Ann Rheum Dis,2017,76(4):1-10.
[23] HJELMERVIK T O R,PETERSEN K,JONASSEN I,et al.Gene expression profiling of minor salivary glands clearly distinguishes primary sjögren's syndrome patients from healthy control subjects[J].Arthritis Rheum,2005,52(5):1534-1544.

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