摘要
目的通过多重生物信息学筛选慢加急性肝衰竭(acute-on-chronic liver failure,ACLF)关键基因及通路,为ACLF分子生物学研究和生物学标志物筛选提供理论依据。方法首先从基因表达数据集(Gene Expression Omnibus,GEO)下载ACLF转录组mRNA微阵列数据集,利用R软件中limma包进行基因表达量差异分析,并通过David数据库对差异基因进行基因本体论(gene ontology,GO)功能富集和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析;利用STRING数据库绘制蛋白质互作(protein-protein interaction,PPI)网络图,Cytoscape软件筛选关键差异基因。结果共筛选得到329个差异表达基因,其中上调基因185个,下调基因144个。GO功能富集分析得到条目385个,包含免疫受体活性、细胞因子受体活性、T细胞受体结合等生物学功能(P<0.05);KEGG通路富集分析筛选到36条信号通路,免疫和炎症相关的通路包括Th1和Th2细胞分化、Th17细胞分化通路、T细胞受体信号通路、原发性免疫缺陷、NF-κB信号通路和TNF信号通路等。进一步得到与ACLF相关的核心差异基因CD3G、CD3D、IL7R、LCK、IL1R2、IL18R1、IL1R1和MAPK14,这些基因可能成为ACLF潜在的生物标志物及治疗靶点。结论本研究发现,CD3G、CD3D、IL7R、LCK、IL1R2、IL18R1、IL1R1和MAPK14可能成为ACLF发生、发展相关核心基因和未来新的治疗靶点。
Objective To screen key genes and pathways of acute on-chronic liver failure(ACLF)by multiple bioinformatics,and to provide theoretical basis for molecular biology studies and biomarker screening of ACLF.Methods ACLF transcriptome mRNA microarray data set was downloaded from Gene Expression Omnibus(GEO),and limma package in R software was used to analyze the difference expression genes.The gene ontology(GO)function enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were analyzed differential genes through David database.Protein-protein interaction(PPI)network was analyzed using STRING database,the key differential genes were screened by Cytoscape software.Results A total of 329differentially expressed genes were screened,including 185 up-regulated genes and 144 down-regulated genes.GO functional enrichment analysis obtained 385 items,including immune receptor activity,cytokine receptor activity,T cell receptor binding and other biological functions(P<0.05).KEGG pathway enrichment analysis screened 36signaling pathways,among which the immune and inflammatory pathways including Th1 and Th2 cell differentiation,Th17 cell differentiation pathway,T cell receptor signaling pathway,primary immune deficiency,NF-κB signaling pathway and TNF signaling pathway.Among these key genes,CD3G,CD3D,IL7R,LCK,IL1R2,IL18R1,IL1R1 and MAPK14 related to ACLF were further obtained,which may become potential biomarkers and therapeutic targets of ACLF.Conclusion This study demonstrates that CD3G,CD3D,IL7R,LCK,IL1R2,IL18R1,IL1R1 and MAPK14may become the core genes related to the occurrence and development of ACLF and new therapeutic targets in the future.
作者
王秀峰
陈桂容
林华明
WANG Xiufeng;CHEN Guirong;LIN Huaming(District 1 of Liver Disease,The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine,Guangxi 530023,China)
出处
《医学研究杂志》
2023年第12期83-88,共6页
Journal of Medical Research
基金
广西自然科学基金资助项目(2018GXNSFBA281031)
广西自然科学基金创新研究团队项目(2018GXNSFGA281002)。
