基于基因测序和GEO数据挖掘探讨结核性溃疡的发病机制  

Exploring the pathogenesis of tuberculous ulcer based on gene sequencing and GEO data mining

作　　者：高贝贝 黄子慧[1] 陈思琪 曹丽敏 翁嘉晨 郭丹丹[1] 陈悦 GAO Bei-bei;HUANG Zi-hui;CHEN Si-qi;CAO Li-min;WENG Jia-chen;GUO Dan-dan;CHEN Yue(Nanjing Integrated Traditional Chinese and Western Medicine Hospital,Nanjing University of Chinese Medicine,Nanjing 210014,China)

机构地区：[1]南京中医药大学附属南京市中西医结合医院,江苏南京210014

出　　处：《中国感染控制杂志》2023年第1期23-30,共8页Chinese Journal of Infection Control

基　　金：江苏省中医药科技发展计划重点项目(ZD202105);许芝银全国名中医专家工作室(宁卫财务[2019]26号);南京市卫健委重点科技项目(ZKX20049)。

摘　　要：目的通过生物信息学途径,挖掘结核性溃疡发生发展过程中的关键基因,为结核性溃疡的研究提供新思路。方法选择课题组前期基因测序的数据集及基因表达综合数据库(GEO)下载的数据集GSE83456,利用R软件筛选出共同的差异表达基因,再对共同的差异基因进行基因本体论(GO)以及京都基因与基因组百科全书(KEGG)富集分析。利用STRING及Cytoscape软件构建蛋白质与蛋白质相互作用(PPI)网络并进行可视性,使用cytoHubba插件进一步筛选出关键基因,用基因组富集分析(GSEA)进行验证。选取2021年7月—2022年3月某院住院的60例结核性溃疡患者及同期60例健康体检人员,利用逆转录聚合酶链反应(qRT-PCR)对血清中的关键基因进行验证。结果筛选出共同的差异表达基因19个,主要富集在抗病毒免疫反应、单核细胞趋化性调节、干扰素-β等功能以及NOD样受体信号通路、感染性疾病等方面。分析PPI后筛选出GBP1作为关键基因,GSEA证实GBP1与结核性溃疡高度相关。qRT-PCR证实GBP1在结核性溃疡患者的血清中高表达,并在治疗2周后明显下降(均P<0.001)。结论GBP1可能成为结核性溃疡诊断的生物学标志物以及治疗的潜在靶点。Objective To explore the key genes in the occurrence and development of tuberculous ulcer(TU)through bioinformatics,and provide new ideas for the study of TU.Methods Datasets of previous acquired gene sequencing and GSE83456 downloaded from gene expression omnibus(GEO)were selected.Common differentially expressed genes were screened by R software and performed enrichment analysis via gene ontology(GO)as well as Kyoto encyclopedia of genes and genomes(KEGG).Protein-protein interaction(PPI)network was constructed and visualized by STRING and Cytoscape software.Key genes were screened out by cytoHubba plug-in,then verified by gene set enrichment analysis(GSEA).60 patients with TU in a hospital from July 2021 to March 2022 and 60 healthy physical examination persons during the same period were selected.Key genes in serum were verified by quantitative reverse transcription-polymerase chain reaction(qRT-PCR).Results 19 common differentially expressed genes were screened out,mainly enriched in antiviral immune response,monocyte chemotaxis regulation,interferon-βfunction,NOD-like receptor signaling pathway,and infectious diseases,etc.GBP1 was screened out as a key gene after PPI analysis,and verified to be highly correlated with TU by GSEA.qRT-PCR confirmed that GBP1 expression was high in the serum of TU patients,and decreased significantly after 2 weeks treatment(both P<0.001).Conclusion GBP1 may be a biomarker for TU diagnosis and potential target for treatment.

关 键 词：结核性溃疡 生物信息学 基因 发病机制 GBP1 

分 类 号：R529.8[医药卫生—内科学]