摘要
目的利用生物信息学方法筛选酒精性脂肪性肝炎(ASH)肝组织与正常肝组织间的差异表达基因,为探索ASH的关键基因和分子机制提供理论依据。方法从基因芯片公共数据库下载ASH基因芯片数据集GSE28619和GSE103580,共包括ASH患者肝组织标本28例,正常肝组织标本7例。使用R软件对芯片数据进行整合并筛选出差异表达基因。采用在线DAVID分析软件对差异表达基因进行基因本体论(GO)富集分析,应用R软件中Clusterprofiler包对差异基因进行KEGG信号途径分析,利用STRING及Cytoscape软件进一步构建蛋白质-蛋白质相互作用(PPI)网络,并利用Cytoscape软件中的CytoHubba插件,综合12种拓扑分析方法筛选出前3个核心基因。结果共筛选出28个差异表达基因,GO富集分析发现,差异表达基因参与了皮质醇反应、Wnt蛋白活性、细胞对细胞外刺激的反应、转录因子活性、转录激活因子活性及RNA聚合酶Ⅱ核心启动子近端区序列特异性结合等功能。KEGG通路分析发现,差异表达基因富集在唯一一个通路——白细胞介素-17(IL-17)信号通路上。PPI分析得到3个核心基因,分别为CCL20、FOS及NR4A2,并且CCL20与FOS均富集在IL-17信号通路上。对PPI网络中的节点进行富集分析发现,其功能主要富集在信号转导上。结论通过生物信息学分析,预测CCL20、FOS及NR4A2可能是介导ASH的核心基因,其中CCL20可能通过作用在IL-17信号通路上,被诱导激活后促进巨噬细胞、中性粒细胞等炎症细胞的募集,从而介导ASH炎症发生。靶向调控IL-17信号通路有望成为ASH治疗的新型疗法。
Objective To identify the differentially expressed genes between liver tissue of alcoholic steatohepatitis(ASH)and normal liver tissue by bioinformatics methods and provide theoretical basis for exploring the key genes and molecular mechanisms of ASH.Methods The ASH gene chip datasets GSE28619 and GSE103580 were downloaded from the Gene Chip Public Database,including 28 liver tissues of ASH patients and 7 normal liver tissues.The R software was used to integrate the chip data and screen for differentially expressed genes.Gene ontology(GO)enrichment analysis was performed by online DAVID analysis software.The KEGG signaling pathway was analyzed by using the Clusterprofiler package in R software.The protein-protein interaction(PPI)network was further constructed by STRING and Cytoscape software.The first three core genes were screened out by using the CycloHubba plug-in in the Cytoscape software and 12 topological analysis methods.Results A total of 28 differentially expressed genes were identified.GO enrichment analysis revealed that they were involved in response to corticosterone,Wnt-protein binding,cellular response to extracellular stimulus,transcription factor activity,RNA polymeraseⅡcore promoter proximal region sequence-specific binding.The KEGG pathway analysis revealed that differential genes were enriched in the only pathway,which was the interleukin-17(IL-17)signaling pathway.PPI analysis showed three core genes,namely CCL20,FOS and NR4A2,and both CCL20 and FOS were enriched in the IL-17 signaling pathway.The enrichment analysis of the nodes found that the main enrichment was on signal transduction.Conclusion Bioinformatics analysis predicts that CCL20,FOS and NR4A2 may be the core genes of ASH.CCL20 may act on the IL-17 signaling pathway and promote the recruitment of inflammatory cells such as macrophages and neutrophils after induction and activation,thereby mediating the occurrence of ASH inflammation.providing new ideas for understanding the molecular mechanism of ASH.IL-17 signaling pathway is e
作者
李毅勤
姜瑶
陶华林
郭永灿
LI Yiqin;JIANG Yao;TAO Hualin;GUO Yongchan(Department of Clinical Laboratory,Affiliated Hospital of Southwest Medical University,Luzhou,Sichuan 646000,China;Department of Clinical Laboratory,Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University,Luzhou,Sichuan 646000,China)
出处
《国际检验医学杂志》
CAS
2020年第15期1839-1843,共5页
International Journal of Laboratory Medicine
基金
西南医科大学青年基金(2018-ZRQN-125)。
