[Bioinformatics screening and analysis of key differentially expressed genes characteristics in nonalcoholic fatty liver disease]

Zhonghua Gan Zang Bing Za Zhi. 2022 Mar 20;30(3):297-303. doi: 10.3760/cma.j.cn501113-20210525-00251.
[Article in Chinese]

Abstract

Objective: To screen and analyze the key differentially expressed genes characteristics in nonalcoholic fatty liver disease (NAFLD) with bioinformatics method. Methods: NAFLD-related expression matrix GSE89632 was downloaded from the GEO database. Limma package was used to screen differentially expressed genes (DEGs) in healthy, steatosis (SS), and nonalcoholic steatohepatitis (NASH) samples. WGCNA was used to analyze the output gene module. The intersection of module genes and differential genes was used to determine the differential genes characteristic, and then GO function and KEGG signaling pathway enrichment analysis were performed. The protein-protein interaction network (PPI) was constructed using the online website STRING and Cytoscape software, and the key (Hub) genes were screened. Finally, R software was used to analyze the receiver operating characteristic curve (ROC) of the Hub gene. Results: 92 differentially expressed genes characteristic were obtained through screening, which were mainly enriched in inflammatory response-related functions of "lipopolysaccharide response and molecular response of bacterial origin", as well as cancer signaling pathways of "proteoglycan in cancer" and "T-cell leukemia virus infection-related". 10 hub genes (FOS, CXCL8, SERPINE1, CYR61, THBS1, FOSL1, CCL2, MYC, SOCS3 and ATF3) had good diagnostic value. Conclusion: The differentially expressed hub genes among the 10 NAFLD disease-related characteristics obtained with bioinformatics analysis may become a diagnostic and prognostic marker and potential therapeutic target for NAFLD. However, further basic and clinical studies are needed to validate.

目的: 应用生物信息学方法筛选和分析非酒精性脂肪性肝病(NAFLD)特征差异表达关键基因。 方法: GEO数据库中下载NAFLD相关的表达矩阵GSE89632,使用Limma包筛选健康样本、脂肪变性(SS)样本和非酒精性脂肪性肝炎(NASH)样本差异表达基因(DEGs),WGCNA分析输出模块基因;模块基因与差异基因取交集确定特征差异基因,随后进行GO功能和KEGG信号通路富集分析。使用在线网站STRING和Cytoscape软件构建蛋白互作网络(PPI),并筛选关键(Hub)基因。最后使用R软件进行Hub基因的受试者操作特征曲线(ROC)分析。 结果: 经筛选共获得92个特征差异表达基因,主要富集于 “脂多糖反应和细菌起源分子反应”的炎症反应相关功能,以及“癌症中蛋白聚糖”和“T细胞白血病病毒感染相关”癌症信号通路。10个Hub基因(FOS,CXCL8,SERPINE1,CYR61,THBS1,FOSL1,CCL2,MYC,SOCS3和ATF3)具有较好的诊断价值。 结论: 通过生物信息学分析获得的10个NAFLD疾病相关特征差异表达Hub基因,可能成为NAFLD的诊断和预后标志物及潜在治疗靶点,有待进一步基础和临床研究验证。.

MeSH terms

  • Computational Biology / methods
  • Gene Expression Profiling / methods
  • Gene Regulatory Networks
  • Humans
  • Non-alcoholic Fatty Liver Disease* / genetics
  • Protein Interaction Maps / genetics