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中华肝脏外科手术学电子杂志

中华肝脏外科手术学电子杂志 ›› 2025, Vol. 14 ›› Issue (05) : 761 -769. doi: 10.3877/cma.j.issn.2095-3232.2025.05.015

基础研究

生物信息学分析内质网应激相关基因在非酒精性脂肪性肝炎发病中的作用
张广权, 洪生杰, 陈显育, 王继才, 翟航, 吴芬芳, 史宪杰†()   
  1. 518000　深圳，中山大学附属第八医院肝胆胰外科
  • 收稿日期:2025-04-08 出版日期:2025-10-10
  • 通信作者: 史宪杰
  • 基金资助:
    广东省基础与应用基础研究基金企业联合基金项目资助(2023A1515220186); 深圳市基础研究资助项目(JCYJ20220530144404010，JCYJ20220530144404011); 深圳市福田区卫生健康系统科研项目资助(FTWS2023037，FTWS050，FTWS049); 福田区重点专科资助(QZDZK-202413); 中山大学附属第八医院优秀医学创新人才计划资助(YXYXCXRC202414)

Bioinformatics analysis of the role of endoplasmic reticulum stress-associated genes in the pathogenesis of nonalcoholic steatohepatitis

Guangquan Zhang, Shengjie Hong, Xianyu Chen, Jicai Wang, Hang Zhai, Fenfang Wu, Xianjie Shi†()   

  1. Department of Hepatobiliary and Pancreatic Surgery, the Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen 518000, China
  • Received:2025-04-08 Published:2025-10-10
  • Corresponding author: Xianjie Shi
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引用本文：

张广权, 洪生杰, 陈显育, 王继才, 翟航, 吴芬芳, 史宪杰. 生物信息学分析内质网应激相关基因在非酒精性脂肪性肝炎发病中的作用[J/OL]. 中华肝脏外科手术学电子杂志, 2025, 14(05): 761-769.

Guangquan Zhang, Shengjie Hong, Xianyu Chen, Jicai Wang, Hang Zhai, Fenfang Wu, Xianjie Shi. Bioinformatics analysis of the role of endoplasmic reticulum stress-associated genes in the pathogenesis of nonalcoholic steatohepatitis[J/OL]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2025, 14(05): 761-769.

目的

利用生物信息学分析方法探索内质网应激（ERS）相关基因在非酒精性脂肪性肝炎（NASH）发展中的潜在作用机制。

方法

本研究从GEO数据库（https://www.ncbi.nlm.nih.gov/geo/）下载基因表达数据集GSE63067。该数据集包含9例NASH患者和7例健康个体的基因表达数据。基于limma软件包的差异表达分析NASH患者与健康对照组间的差异表达基因。采用基因本体（GO）功能分析、KEGG通路富集分析和蛋白质相互作用（PPI）网络构建等方法分析ERS相关差异表达基因在NASH发病中的潜在功能。

结果

共鉴定出14个ERS相关的差异表达基因，其中BIRC3、CASP4、CASP7、FABP5、LECT2、PHLDA1、SGK1、TSLP、SGMS2、NAMPT、IRF1和CD274等12个基因在NASH中表达上调，而CEBPA和IGFBP2表达下调。GO功能分析显示，差异表达基因主要参与NASH发病过程中细胞因子信号通路、细胞凋亡、T细胞增殖调控、细胞活化等相关的生物学过程。KEGG通路分析表明，差异表达基因主要参与TNF信号通路、多物种凋亡通路、核苷酸结合寡聚化结构域（NOD）样受体信号通路、BioCarta IL-1R通路、Hinata NF-κB靶向角质形成细胞上调通路、Marzec IL-2信号上调通路以及Mense缺氧上调通路。PPI网络分析进一步揭示了这些基因之间的潜在相互作用。

结论

ERS相关差异表达基因参与了NASH发病相关的细胞因子信号通路、细胞凋亡、免疫调节和炎症反应等多个生物学过程，为进一步探讨ERS在NASH发病机制中的作用提供了新的线索。

关键词: 非酒精性脂肪性肝病, 内质网应激, 生物信息学分析, 治疗靶点
Objective

To investigate the underlying mechanism of endoplasmic reticulum stress (ERS)-associated genes in the progression of nonalcoholic steatohepatitis (NASH) by bioinformatics analysis.

Methods

The GSE63067 dataset was downloaded from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). This dataset contains gene expression data of 9 patients with NASH and 7 healthy individuals. Differentially expressed genes between NASH patients and healthy controls were analyzed based on limma software package. Based on bioinformatics analyses, such as Gene Ontology (GO) functional analysis, KEGG pathway enrichment analysis and protein-protein interaction (PPI) network construction, the potential function of ERS-associated differentially expressed genes in the pathogenesis of NASH was illustrated.

Results

14 ERS-associated differentially expressed genes were identified. Among them, the expression levels of 12 genes including BIRC3, CASP4, CASP7, FABP5, LECT2, PHLDA1, SGK1, TSLP, SGMS2, NAMPT, IRF1 and CD274 were up-regulated, whereas those of CEBPA and IGFBP2 were down-regulated in NASH. GO functional analysis showed that differentially expressed genes were mainly involved in cytokine signaling pathway, apoptosis, T cell proliferation regulation, cell activation and other related biological processes in the pathogenesis of NASH. KEGG pathway analysis demonstrated that differentially expressed genes were mainly involved in TNF signaling pathway, multi-species apoptosis pathway, nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway, BioCarta IL-1R pathway, Hinata NF-κB-targeted keratinocyte up-regulation pathway, Marzec IL-2 signal up-regulation pathway and Mense hypoxia up-regulation pathway. PPI network analysis further revealed potential interaction among these genes.

Conclusions

ERS-associated differentially expressed genes are involved in multiple biological processes related to the pathogenesis of NASH, such as cytokine signaling pathway, apoptosis, immune regulation and inflammatory reaction, providing novel clues for further unravelling the role of ERS in the pathogenesis of NASH.

Key words: Non-alcoholic fatty liver disease, Endoplasmic reticulum stress, Bioinformatics analysis, Therapeutic targets
图1 NASH和健康组中ERS相关基因的差异表达 注：a为GSE63067数据集的主成分分析；b为差异表达基因的火山图；c为NASH与健康组ERS相关基因的差异表达热图；ERS为内质网应激，NASH为非酒精性脂肪性肝炎，PC为主成分
图2 ERS相关基因在NASH和健康组中的差异表达 注：ERS为内质网应激，NASH为非酒精性脂肪性肝炎
图3 ERS相关差异表达基因的PPI网络 注：ERS为内质网应激，PPI为蛋白质-蛋白质相互作用
图4 ERS相关差异表达基因Spearman相关性分析 注：ERS为内质网应激
图5 ERS相关差异表达基因的GO功能分析 注：ERS为内质网应激，GO为基因本体，BP为生物过程，MF为分子功能
图6 ERS相关差异表达基因的KEGG通路富集分析 注：a为BioCarta IL-1R通路富集结果；b为Hinata NF-κB靶向角质形成细胞上调通路富集结果；c为Marzec IL-2信号上调通路富集结果；d为Mense缺氧上调通路富集结果；ERS为内质网应激
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你好！我是《中华医学电子期刊资源库》AI小编，有什么可以帮您的吗？