中国医药导报2024,Vol.21Issue(13) :29-33.DOI:10.20047/j.issn1673-7210.2024.13.06

基于生物信息学对非酒精性脂肪性肝病肝纤维化进展关键基因的挖掘与分析

Mining and analysis of hub genes in hepatic fibrosis progression of non-alcoholic fatty liver disease based on bioinformatics

梁金强 任松 花欣
中国医药导报2024,Vol.21Issue(13) :29-33.DOI:10.20047/j.issn1673-7210.2024.13.06

基于生物信息学对非酒精性脂肪性肝病肝纤维化进展关键基因的挖掘与分析

Mining and analysis of hub genes in hepatic fibrosis progression of non-alcoholic fatty liver disease based on bioinformatics

梁金强 1任松 1花欣2
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作者信息

  • 1. 西安交通大学第二附属医院干部病房普通外科,陕西西安 710004
  • 2. 西安市人民医院 西安市第四医院医学影像中心,陕西西安 710004
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摘要

目的 基于生物信息学分析对非酒精性脂肪性肝病(NAFLD)肝纤维化进展关键基因及潜在致病机制进行挖掘.方法 从GEO数据库获取数据集GSE49541,limma包筛选出差异表达基因(DEGs)后对其进行基因本体(GO)功能注释及京都基因与基因组百科全书(KEGG)通路分析.STRING数据库对DEGs构建蛋白质-蛋白质相互作用网络,并用Cytoscape筛选关键基因,利用Gene MANIA分析关键基因的共表达网络和功能,最后基于药物特征数据库对关键基因进行药物预测.结果 进展期NAFLD与轻度NAFLD比较后,DEGs有65个,表达上调的基因58个,表达下调的基因7个.GO功能分析强调了 65个DEGs的分子功能集中在细胞外基质结构成分,KEGG通路分析显示,DEGs主要与细胞外基质受体相互反应等通路有关.Cytoscape筛选出的10个关键基因为COL1A1、COL3A1、COL4A1、COL1A2、COL14A1、FBN1、LUM、THBS1、THBS2、SPP1.Gene MANIA提示关键基因之间存在高度的共表达-互作网络,与细胞外基质结构成分等功能相关.最后,药物预测分析发现,维甲酸和黄体酮是富集到最多关键基因的药物.结论 NAFLD纤维化进展相关的10个关键基因可能成为其生物监测标志物并为分子靶向治疗提供线索.

Abstract

Objective To explore the hub genes and potential pathogenesis of hepatic fibrosis in non-alcoholic fatty liver disease based on bioinformatics analysis.Methods Dataset GSE49541 was obtained from GEO database.Differentially expressed genes(DEGs)were screened out in limma package,and their gene ontology(GO)function annotation and Kyoto encyclopedia of genes and genomes(KEGG)pathway analysis were performed.The protein protein interaction network was constructed by STRING database on DEGs,and key genes were screened by Cytoscape.The co-expression network and function of hub genes were analyzed using Gene MANIA.Finally,drug prediction of key genes was performed based on drug signature database.Results In advanced stage NAFLD and mild NAFLD after comparison,there were a total of 65 DEGs,with 58 genes upregulated and 7 genes downregulated.GO functional analysis highlights that the molecular functions of these 65 DEGs were primarily concentrated in extracellular matrix structure components.KEGG pathway analysis shows that DEGs were mainly associated with pathways involving interactions with extracellular matrix receptors.Cytoscape analysis has identified ten key genes,namely COL1A1,COL3A1,COL4A1,COL1A2,COL14A1,FBN1,LUM,THBS1,THBS2,and SPP1.Gene MANIA suggests a highly interconnected co-expression and interaction network among these key genes,related to functions such as extracellular matrix structure components.Finally,drug prediction analysis reveals that Retinoic Acid and Progesterone are the drugs most enriched with the highest number of key genes.Conclusion Ten hub genes associated with NAFLD fibrosis progression were identified by bioinformatics which could be biomarkers for its biological monitoring and providing clues for molecular targeted therapy.

关键词

非酒精性脂肪性肝病/肝纤维化/关键基因/生物信息学

Key words

Non-alcoholic fatty liver disease/Liver fibrosis/Hub genes/Bioinformatics

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基金项目

陕西省重点研发计划(2020SF-298)

出版年

2024
中国医药导报
中国医学科学院

中国医药导报

CSTPCD
影响因子:1.759
ISSN:1673-7210
参考文献量28
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