Xibing Zhang, Fuli Yang, Lei Han, Qiuming Su, Yang Gao, Ruichao Wu, Duo Wang, Wang Li, Kepu Zheng, Fang Liu, Jianghua Ran
{"title":"Identification of pivotal genes and crucial pathways in liver fibrosis through WGCNA analysis.","authors":"Xibing Zhang, Fuli Yang, Lei Han, Qiuming Su, Yang Gao, Ruichao Wu, Duo Wang, Wang Li, Kepu Zheng, Fang Liu, Jianghua Ran","doi":"10.3233/THC-241142","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Liver fibrosis is a progressive liver disease with increasing incidence, yet its underlying pathogenic mechanisms remain incompletely understood.</p><p><strong>Objective: </strong>: This study aims to explore potential therapeutic targets for liver fibrosis using weighted gene co-expression network analysis (WGCNA) and experimental validation.</p><p><strong>Methods: </strong>We retrieved the microarray data (GSE174099) from the GEO database and performed differential expression analysis and WGCNA to identify co-expression modules associated with liver fibrosis. A module with the highest correlation to liver fibrosis was selected for further analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to investigate the biological functions and signaling pathways of the identified genes. Protein-protein interaction (PPI) networks were constructed using the STRING database. The correlation between core genes and immune cells was analyzed with the CIBERSORT algorithm. Additionally, pathological and molecular biology experiments were performed to validate the expression levels of core genes in liver tissue, including HE and Masson staining, immunohistochemistry, RT-qPCR, and Western blotting.</p><p><strong>Results: </strong>We identified a total of 86 intersecting genes from the differential expression analysis and WGCNA. GO enrichment analysis revealed that these genes were involved in processes such as cellular response to cAMP, collagen-containing extracellular matrix, and G protein-coupled receptor binding. KEGG pathway analysis highlighted the involvement of these genes in pathways like Cell Adhesion Molecules and the PI3K-Akt signaling pathway. Using Cytoscape software, we identified four core genes: Cftr, Cldn4, Map2, and Spp1. Pathological examinations showed that the experimental group exhibited significant fibrous tissue proliferation compared to the control group. Immunohistochemistry, RT-qPCR, and Western blotting analyses confirmed that these core genes were significantly upregulated in the experimental group (P< 0.05).</p><p><strong>Conclusion: </strong>This study identified four key genes (Cftr, Cldn4, Map2, Spp1) that are significantly associated with liver fibrosis. These genes are upregulated in liver fibrosis and could potentially as biomarkers for diagnosis and targets for therapeutic interventions.</p>","PeriodicalId":48978,"journal":{"name":"Technology and Health Care","volume":" ","pages":"431-448"},"PeriodicalIF":1.4000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Technology and Health Care","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.3233/THC-241142","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Liver fibrosis is a progressive liver disease with increasing incidence, yet its underlying pathogenic mechanisms remain incompletely understood.
Objective: : This study aims to explore potential therapeutic targets for liver fibrosis using weighted gene co-expression network analysis (WGCNA) and experimental validation.
Methods: We retrieved the microarray data (GSE174099) from the GEO database and performed differential expression analysis and WGCNA to identify co-expression modules associated with liver fibrosis. A module with the highest correlation to liver fibrosis was selected for further analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to investigate the biological functions and signaling pathways of the identified genes. Protein-protein interaction (PPI) networks were constructed using the STRING database. The correlation between core genes and immune cells was analyzed with the CIBERSORT algorithm. Additionally, pathological and molecular biology experiments were performed to validate the expression levels of core genes in liver tissue, including HE and Masson staining, immunohistochemistry, RT-qPCR, and Western blotting.
Results: We identified a total of 86 intersecting genes from the differential expression analysis and WGCNA. GO enrichment analysis revealed that these genes were involved in processes such as cellular response to cAMP, collagen-containing extracellular matrix, and G protein-coupled receptor binding. KEGG pathway analysis highlighted the involvement of these genes in pathways like Cell Adhesion Molecules and the PI3K-Akt signaling pathway. Using Cytoscape software, we identified four core genes: Cftr, Cldn4, Map2, and Spp1. Pathological examinations showed that the experimental group exhibited significant fibrous tissue proliferation compared to the control group. Immunohistochemistry, RT-qPCR, and Western blotting analyses confirmed that these core genes were significantly upregulated in the experimental group (P< 0.05).
Conclusion: This study identified four key genes (Cftr, Cldn4, Map2, Spp1) that are significantly associated with liver fibrosis. These genes are upregulated in liver fibrosis and could potentially as biomarkers for diagnosis and targets for therapeutic interventions.
期刊介绍：
Technology and Health Care is intended to serve as a forum for the presentation of original articles and technical notes, observing rigorous scientific standards. Furthermore, upon invitation, reviews, tutorials, discussion papers and minisymposia are featured. The main focus of THC is related to the overlapping areas of engineering and medicine. The following types of contributions are considered:
1.Original articles: New concepts, procedures and devices associated with the use of technology in medical research and clinical practice are presented to a readership with a widespread background in engineering and/or medicine. In particular, the clinical benefit deriving from the application of engineering methods and devices in clinical medicine should be demonstrated. Typically, full length original contributions have a length of 4000 words, thereby taking duly into account figures and tables.
2.Technical Notes and Short Communications: Technical Notes relate to novel technical developments with relevance for clinical medicine. In Short Communications, clinical applications are shortly described. 3.Both Technical Notes and Short Communications typically have a length of 1500 words.
Reviews and Tutorials (upon invitation only): Tutorial and educational articles for persons with a primarily medical background on principles of engineering with particular significance for biomedical applications and vice versa are presented. The Editorial Board is responsible for the selection of topics.
4.Minisymposia (upon invitation only): Under the leadership of a Special Editor, controversial or important issues relating to health care are highlighted and discussed by various authors.
5.Letters to the Editors: Discussions or short statements (not indexed).
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