摘要
目的 通过生物信息学数据探讨肺结核(pulmonary tuberculosis, PTB)发病机制,为肺结核的形成和发展提供理论依据。方法 从GEO数据库中下载肺结核的基因表达谱数据,通过GEO2R对数据集进行在线分析并筛选差异表达基因,进一步对共同差异表达基因并进行GO、KEGG富集分析和蛋白互作分析,通过ELISA法检测并比较活动期肺结核、潜伏期肺结核及健康对照中目的蛋白表达水平的差异。结果 GSE83456数据集中,PTB组中显著上调的基因共有1 621个,显著下调的基因有754个,GSE34608数据集中,PTB组中显著上调的基因共有1 468个,显著下调的基因有1 902个。筛选后获得21个共同差异表达基因,主要富集于蛋白结合、病毒免疫防御、免疫应答、固有免疫及NOD样受体信号通路等。蛋白互作分析后筛选出9个核心基因如IDO1、GBP1、GBP5、IFIT2、PSAD2、CARD17、CARD16、EPSTI1和AIM2。GBP1、GBP5和AIM2蛋白表达水平在对照组、潜伏期肺结核组和活动期肺结核组中依次升高,两两比较差异有统计学意义(P<0.05)。GBP1、GBP5和AIM2在鉴别活动期和潜伏期肺结核的曲线下面积分别为0.911、0.879和0.815,3种指标均具有较高的鉴别敏感度和特异度。结论 多种基因共同参与了PTB的发生发展,GBP1、GBP5和AIM2可能是PTB最相关的特征基因。
Objective This paper aims to explore the pathogenesis of pulmonary tuberculosis(PTB)through bioinformatics data,so as to provide theoretical basis for the formation and development of pulmonary tuberculosis.Methods The gene expression profile data of PTB were downloaded from the GEO database.The GEO2R online database was used to screen the differentially expressed genes.The common differentially expressed genes were further conducted for GO and KEGG enrichment analysis and protein interaction analysis.The differences of target protein expression in active pulmonary tuberculosis,latent pulmonary tuberculosis and healthy controls were detected and compared by enzyme-linked immunosorbent assay(ELISA).Results In GSE83456,a total of 1621 genes were significantly up-regulated and 754 genes were significantly down-regulated in PTB group.In GSE34608,a total of 1468 genes were significantly up-regulated and 1902 genes were significantly down-regulated in PTB group.21 common differentially expressed genes were screened,which were mainly enriched in protein binding,viral immune defense,immune response,innate immunity and NOD-like receptor signaling pathways.After protein interaction analysis,9 hub genes were screened,including IDO1,GBP1,GBP5,IFIT2,PSAD2,CARD17,CARD16,EPSTI1 and AIM2.The protein levels of GBP1,GBP5 and AIM2 between control group,latent pulmonary group and active pulmonary tuberculosis group were compared and the differences were statistically significant(P<0.05).The areas under the curve of GBP1,GBP5 and AIM2 in the identification of active and latent pulmonary tuberculosis were 0.911,0.879 and 0.815,respectively.All the indexes had higher sensitivity and specificity.Conclusion Multiple genes were involved in the occurrence and development of PTB.GBP1,GBP5 and AIM2 may be the most relevant characteristic genes of PTB.
作者
谭磊
张边防
史珂
赵桂增
TAN Lei;ZHANG Bian-fang;SHI Ke;ZHAO Gui-zeng(Department of Tuberculosis,the First Affiliated Hospital of Xinxiang Medical University,Henan 453100,China)
出处
《中国卫生检验杂志》
CAS
2023年第19期2361-2365,共5页
Chinese Journal of Health Laboratory Technology
基金
新乡医学院结核病研究所开放课题(XYJHB202107)。
关键词
肺结核
差异表达基因
富集分析
蛋白互作分析
诊断效能
Pulmonary tuberculosis
Differentially expressed gene
Enrichment analysis
Protein interaction analysis
Diagnostic effectiveness
作者简介
谭磊(1980-),男,硕士,主治医师,主要从事耐多药肺结核临床诊疗工作。
