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

doi:10.3877/cma.j.issn.2095-3232.2025.05.015

Abstract

Abstract:

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

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]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2025, 14(05): 761-769.

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References 43

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