Hub genes, diagnostic model, and predicted drugs in systemic sclerosis by integrated bioinformatics analysis
Background: Systemic sclerosis (scleroderma; SSc), a rare and heterogeneous connective tissue disease, remains unclear in terms of its underlying causative genes and effective therapeutic approaches. The purpose of the present study was to identify hub genes, diagnostic markers and explore potential...
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| Format: | Article |
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1202561/full |
| _version_ | 1827902993016553472 |
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| author | Yue-Mei Yan Meng-Zhu Jin Sheng-Hua Li Yun Wu Qiang Wang Fei-Fei Hu Chen Shen Wen-Hao Yin |
| author_facet | Yue-Mei Yan Meng-Zhu Jin Sheng-Hua Li Yun Wu Qiang Wang Fei-Fei Hu Chen Shen Wen-Hao Yin |
| author_sort | Yue-Mei Yan |
| collection | DOAJ |
| description | Background: Systemic sclerosis (scleroderma; SSc), a rare and heterogeneous connective tissue disease, remains unclear in terms of its underlying causative genes and effective therapeutic approaches. The purpose of the present study was to identify hub genes, diagnostic markers and explore potential small-molecule drugs of SSc.Methods: The cohorts of data used in this study were downloaded from the Gene Expression Complex (GEO) database. Integrated bioinformatic tools were utilized for exploration, including Weighted Gene Co-Expression Network Analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) regression, gene set enrichment analysis (GSEA), Connectivity Map (CMap) analysis, molecular docking, and pharmacokinetic/toxicity properties exploration.Results: Seven hub genes (THY1, SULF1, PRSS23, COL5A2, NNMT, SLCO2B1, and TIMP1) were obtained in the merged gene expression profiles of GSE45485 and GSE76885. GSEA results have shown that they are associated with autoimmune diseases, microorganism infections, inflammatory related pathways, immune responses, and fibrosis process. Among them, THY1 and SULF1 were identified as diagnostic markers and validated in skin samples from GSE32413, GSE95065, GSE58095 and GSE125362. Finally, ten small-molecule drugs with potential therapeutic effects were identified, mainly including phosphodiesterase (PDE) inhibitors (BRL-50481, dipyridamole), TGF-β receptor inhibitor (SB-525334), and so on.Conclusion: This study provides new sights into a deeper understanding the molecular mechanisms in the pathogenesis of SSc. More importantly, the results may offer promising clues for further experimental studies and novel treatment strategies. |
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| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-13T00:07:00Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj.art-a43c8f2dbd2e48238a2fd0595c9895a22023-07-13T00:29:07ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-07-011410.3389/fgene.2023.12025611202561Hub genes, diagnostic model, and predicted drugs in systemic sclerosis by integrated bioinformatics analysisYue-Mei Yan0Meng-Zhu Jin1Sheng-Hua Li2Yun Wu3Qiang Wang4Fei-Fei Hu5Chen Shen6Wen-Hao Yin7Department of Dermatology, The First Hospital of Jiaxing, The Affiliated Hospital of Jiaxing University, Jiaxing, ChinaDepartment of Dermatology, The First Hospital of Jiaxing, The Affiliated Hospital of Jiaxing University, Jiaxing, ChinaDepartment of Dermatology, The First Hospital of Jiaxing, The Affiliated Hospital of Jiaxing University, Jiaxing, ChinaDepartment of Dermatology, The First Hospital of Jiaxing, The Affiliated Hospital of Jiaxing University, Jiaxing, ChinaDepartment of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Dermatology, Shanghai Skin Disease Hospital, Tongji University, Shanghai, ChinaDepartment of Dermatology, The First Hospital of Jiaxing, The Affiliated Hospital of Jiaxing University, Jiaxing, ChinaBackground: Systemic sclerosis (scleroderma; SSc), a rare and heterogeneous connective tissue disease, remains unclear in terms of its underlying causative genes and effective therapeutic approaches. The purpose of the present study was to identify hub genes, diagnostic markers and explore potential small-molecule drugs of SSc.Methods: The cohorts of data used in this study were downloaded from the Gene Expression Complex (GEO) database. Integrated bioinformatic tools were utilized for exploration, including Weighted Gene Co-Expression Network Analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) regression, gene set enrichment analysis (GSEA), Connectivity Map (CMap) analysis, molecular docking, and pharmacokinetic/toxicity properties exploration.Results: Seven hub genes (THY1, SULF1, PRSS23, COL5A2, NNMT, SLCO2B1, and TIMP1) were obtained in the merged gene expression profiles of GSE45485 and GSE76885. GSEA results have shown that they are associated with autoimmune diseases, microorganism infections, inflammatory related pathways, immune responses, and fibrosis process. Among them, THY1 and SULF1 were identified as diagnostic markers and validated in skin samples from GSE32413, GSE95065, GSE58095 and GSE125362. Finally, ten small-molecule drugs with potential therapeutic effects were identified, mainly including phosphodiesterase (PDE) inhibitors (BRL-50481, dipyridamole), TGF-β receptor inhibitor (SB-525334), and so on.Conclusion: This study provides new sights into a deeper understanding the molecular mechanisms in the pathogenesis of SSc. More importantly, the results may offer promising clues for further experimental studies and novel treatment strategies.https://www.frontiersin.org/articles/10.3389/fgene.2023.1202561/fullsystemic sclerosisweighted gene co-expression network analysisconnectivity mapmolecular dockingphosphodiesterase inhibitors |
| spellingShingle | Yue-Mei Yan Meng-Zhu Jin Sheng-Hua Li Yun Wu Qiang Wang Fei-Fei Hu Chen Shen Wen-Hao Yin Hub genes, diagnostic model, and predicted drugs in systemic sclerosis by integrated bioinformatics analysis Frontiers in Genetics systemic sclerosis weighted gene co-expression network analysis connectivity map molecular docking phosphodiesterase inhibitors |
| title | Hub genes, diagnostic model, and predicted drugs in systemic sclerosis by integrated bioinformatics analysis |
| title_full | Hub genes, diagnostic model, and predicted drugs in systemic sclerosis by integrated bioinformatics analysis |
| title_fullStr | Hub genes, diagnostic model, and predicted drugs in systemic sclerosis by integrated bioinformatics analysis |
| title_full_unstemmed | Hub genes, diagnostic model, and predicted drugs in systemic sclerosis by integrated bioinformatics analysis |
| title_short | Hub genes, diagnostic model, and predicted drugs in systemic sclerosis by integrated bioinformatics analysis |
| title_sort | hub genes diagnostic model and predicted drugs in systemic sclerosis by integrated bioinformatics analysis |
| topic | systemic sclerosis weighted gene co-expression network analysis connectivity map molecular docking phosphodiesterase inhibitors |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1202561/full |
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