摘要
目的通过采用生物信息学方法挖掘活动性结核生物标志物,提高活动性结核诊断效率。方法登陆GEO数据库下载基因表达芯片GSE19491、GSE25534和GSE31348。采用在线分析工具GEO2R对GSE19491和GSE25534两组芯片数据进行分析,筛选活动性结核感染与正常组织或潜伏结核感染(LTBI)之间的差异表达基因,通过取交集获取核心基因。通过Metascape进行核心基因功能分析,并通过STRING 11.0进行核心基因编码蛋白的相互作用分析。提取活动性肺结核患者GSE31348芯片中核心基因的表达数据,验证核心基因作为活动性结核标志物的有效性。结果通过差异分析取GSE19491和GSE25534两组芯片交集基因,该研究共获得核心基因13个,包括AIM2、ANKRD22、BATF2、C1QB、CARD17、CD274、EPSTI1、ETV7、FCGR1B、GBP1、GBP5、P2RY14和RSAD2。通过功能富集,发现这些核心基因的功能主要与细胞因子的分泌、细胞对γ-干扰素的反应、适应性免疫和细菌感染反应等相关,而信号通路为固有免疫中的NOD样受体相关信号通路。进一步验证这些核心基因在肺结核患者抗结核治疗前后的表达情况,结果显示所有核心基因表达水平在患者接受抗结核治疗后均有不同程度下降,尤其是在抗结核治疗后26周下降幅度最为明显。结论该研究所筛选出来的核心基因AIM2、ANKRD22、BATF2、C1QB、CARD17、CD274、EPSTI1、ETV7、FCGR1B、GBP1、GBP5、P2RY14和RSAD2能够作为反映活动性结核的指标,将这些标志物结合,临床有望提高活动性结核的诊断效率。
Objective To improve the diagnosis efficiency of active tuberculosis,bioinformatics was used to explore the biomarkers of tuberculosis infection in this study.Methods Gene expression chips GSE19491,GSE25534 and GSE31348 from GEO database were downloaded.The differentially expressed genes between active tuberculosis infection and normal tissue or latent tuberculosis infection were analyzed by online analysis tool GEO2R.Core genes were obtained through the intersection of two sets of differentially expressed genes.Core gene function analysis was conducted by Metascape and interaction analysis of core gene coding proteins were conducted by STRING11.0.The expression data of the concentrated core genes in GSE31348 microarray of tuberculosis patients were extracted to verify the effectiveness of the core gene as a marker of active tuberculosis.Results In this study,13 core genes were obtained through differential analysis between gene expression chips GSE19491 and GSE25534,including AIM2,ANKRD22,BATF2,C1QB,CARD17,CD274,EPSTI1,ETV7,FCGR1B,GBP1,GBP5,P2RY14 and RSAD2.Through functional enrichment,it was found that the functions of these core genes were mainly related to cytokine secretion,cellular response to interferon-γ,adaptive immune response and response to bacterium.The signaling pathway was related to NOD-like receptor signaling pathway in the innate immunity.The expression levels of these core genes were further verified before and after anti-tuberculosis treatment in patients with tuberculosis.The results showed that the expression levels of all core genes decreased after patients received anti-tuberculosis treatment,especially in the 26th week,the expression levels decreased significantly.Conclusion The core genes including AIM2,ANKRD22,BATF2,C1QB,CARD17,CD274,EPSTI1,ETV7,FCGR1B,GBP1,GBP5,P2RY14 and RSAD2 could be used as indicators to indicate the activity of tuberculosis.Combining these markers with clinical practice is expected to improve the diagnostic efficiency of active tuberculosis.
作者
洪佳
李汛
HONG Jia;LI Xun(Department of Obstetrics and Gynecology,Renmin Hospital of Wuhan University,Wuhan,Hubei 430060,China;Department of Infectious Diseases,Renmin Hospital of Wuhan University,Wuhan,Hubei 430060,China)
出处
《国际检验医学杂志》
CAS
2020年第16期1983-1986,1990,共5页
International Journal of Laboratory Medicine
基金
武汉大学青年教师资助项目(2042017kf0112)。
