Identification of key genes and pathways in mild and severe nonalcoholic fatty liver disease by integrative analysis

Background: The global prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing. The pathogenesis of NAFLD is multifaceted, and the underlying mechanisms are elusive. We conducted data mining analysis to gain a better insight into the disease and to identify the hub genes associated with...

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Autores principales:	Jin Feng, Tianjiao Wei, Xiaona Cui, Rui Wei, Tianpei Hong
Formato:	article
Lenguaje:	EN
Publicado:	KeAi Communications Co., Ltd. 2021
Materias:	Nonalcoholic fatty liver disease Fatty liver Computational biology Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/1a8a42ed4ab84a138742844cecc25413
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spelling	oai:doaj.org-article:1a8a42ed4ab84a138742844cecc254132021-12-02T18:04:06ZIdentification of key genes and pathways in mild and severe nonalcoholic fatty liver disease by integrative analysis2095-882X10.1016/j.cdtm.2021.08.002https://doaj.org/article/1a8a42ed4ab84a138742844cecc254132021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2095882X21000517https://doaj.org/toc/2095-882XBackground: The global prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing. The pathogenesis of NAFLD is multifaceted, and the underlying mechanisms are elusive. We conducted data mining analysis to gain a better insight into the disease and to identify the hub genes associated with the progression of NAFLD. Methods: The dataset GSE49541, containing the profile of 40 samples representing mild stages of NAFLD and 32 samples representing advanced stages of NAFLD, was acquired from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using the R programming language. The Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database were used to perform the enrichment analysis and construct protein–protein interaction (PPI) networks, respectively. Subsequently, transcription factor networks and key modules were identified. The hub genes were validated in a mice model of high fat diet (HFD)-induced NAFLD and in cultured HepG2 cells by real-time quantitative PCR. Results: Based on the GSE49541 dataset, 57 DEGs were selected and enriched in chemokine activity and cellular component, including the extracellular region. Twelve transcription factors associated with DEGs were indicated from PPI analysis. Upregulated expression of five hub genes (SOX9, CCL20, CXCL1, CD24, and CHST4), which were identified from the dataset, was also observed in the livers of HFD-induced NAFLD mice and in HepG2 cells exposed to palmitic acid or advanced glycation end products. Conclusion: The hub genes SOX9, CCL20, CXCL1, CD24, and CHST4 are involved in the aggravation of NAFLD. Our results offer new insights into the underlying mechanism of NAFLD progression.Jin FengTianjiao WeiXiaona CuiRui WeiTianpei HongKeAi Communications Co., Ltd.articleNonalcoholic fatty liver diseaseFatty liverComputational biologyMedicine (General)R5-920ENChronic Diseases and Translational Medicine, Vol 7, Iss 4, Pp 276-286 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Nonalcoholic fatty liver disease Fatty liver Computational biology Medicine (General) R5-920
spellingShingle	Nonalcoholic fatty liver disease Fatty liver Computational biology Medicine (General) R5-920 Jin Feng Tianjiao Wei Xiaona Cui Rui Wei Tianpei Hong Identification of key genes and pathways in mild and severe nonalcoholic fatty liver disease by integrative analysis
description	Background: The global prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing. The pathogenesis of NAFLD is multifaceted, and the underlying mechanisms are elusive. We conducted data mining analysis to gain a better insight into the disease and to identify the hub genes associated with the progression of NAFLD. Methods: The dataset GSE49541, containing the profile of 40 samples representing mild stages of NAFLD and 32 samples representing advanced stages of NAFLD, was acquired from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using the R programming language. The Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database were used to perform the enrichment analysis and construct protein–protein interaction (PPI) networks, respectively. Subsequently, transcription factor networks and key modules were identified. The hub genes were validated in a mice model of high fat diet (HFD)-induced NAFLD and in cultured HepG2 cells by real-time quantitative PCR. Results: Based on the GSE49541 dataset, 57 DEGs were selected and enriched in chemokine activity and cellular component, including the extracellular region. Twelve transcription factors associated with DEGs were indicated from PPI analysis. Upregulated expression of five hub genes (SOX9, CCL20, CXCL1, CD24, and CHST4), which were identified from the dataset, was also observed in the livers of HFD-induced NAFLD mice and in HepG2 cells exposed to palmitic acid or advanced glycation end products. Conclusion: The hub genes SOX9, CCL20, CXCL1, CD24, and CHST4 are involved in the aggravation of NAFLD. Our results offer new insights into the underlying mechanism of NAFLD progression.
format	article
author	Jin Feng Tianjiao Wei Xiaona Cui Rui Wei Tianpei Hong
author_facet	Jin Feng Tianjiao Wei Xiaona Cui Rui Wei Tianpei Hong
author_sort	Jin Feng
title	Identification of key genes and pathways in mild and severe nonalcoholic fatty liver disease by integrative analysis
title_short	Identification of key genes and pathways in mild and severe nonalcoholic fatty liver disease by integrative analysis
title_full	Identification of key genes and pathways in mild and severe nonalcoholic fatty liver disease by integrative analysis
title_fullStr	Identification of key genes and pathways in mild and severe nonalcoholic fatty liver disease by integrative analysis
title_full_unstemmed	Identification of key genes and pathways in mild and severe nonalcoholic fatty liver disease by integrative analysis
title_sort	identification of key genes and pathways in mild and severe nonalcoholic fatty liver disease by integrative analysis
publisher	KeAi Communications Co., Ltd.
publishDate	2021
url	https://doaj.org/article/1a8a42ed4ab84a138742844cecc25413
work_keys_str_mv	AT jinfeng identificationofkeygenesandpathwaysinmildandseverenonalcoholicfattyliverdiseasebyintegrativeanalysis AT tianjiaowei identificationofkeygenesandpathwaysinmildandseverenonalcoholicfattyliverdiseasebyintegrativeanalysis AT xiaonacui identificationofkeygenesandpathwaysinmildandseverenonalcoholicfattyliverdiseasebyintegrativeanalysis AT ruiwei identificationofkeygenesandpathwaysinmildandseverenonalcoholicfattyliverdiseasebyintegrativeanalysis AT tianpeihong identificationofkeygenesandpathwaysinmildandseverenonalcoholicfattyliverdiseasebyintegrativeanalysis
_version_	1718378674813665280

Identification of key genes and pathways in mild and severe nonalcoholic fatty liver disease by integrative analysis

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