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pmid:33680092

Candidate Genes Identified in Systemic Sclerosis-Related Pulmonary Arterial Hypertension Were Associated with Immunity, Inflammation, and Cytokines.

Zhixiao Xu · Jiaxing Ruan · Lingyun Pan · Chengshui Chen

Cardiovascular therapeutics · 2021 doi:10.1155/2021/6651009

Paper

complete

Experiment

complete

Data

partial

Analysis

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Execution

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:33680092
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title
Candidate Genes Identified in Systemic Sclerosis-Related Pulmonary Arterial Hypertension Were Associated with Immunity, Inflammation, and Cytokines.
doi
10.1155/2021/6651009
pmid
33680092
authors array · 4 items
[0]
Zhixiao Xu
[1]
Jiaxing Ruan
[2]
Lingyun Pan
[3]
Chengshui Chen
journal
Cardiovascular therapeutics
year
2021
abstract
BACKGROUND: Pulmonary complications of systemic sclerosis (SSc), including pulmonary arterial hypertension (PAH), are the leading causes of patient death. However, the precise molecular mechanisms of its etiology are unclear. This study's objective was to identify the candidate genes involved in the progression of SSc-PAH and investigate the genes' function. METHODS: The gene expression profiles of GSE33463 were obtained from the Gene Expression Omnibus (GEO) database. A free-scale gene coexpression network was constructed using the weighted gene coexpression network analysis (WGCNA) to explore the association between gene sets and clinical features and identify candidate biomarkers. Then, gene ontology analysis was performed. A second dataset was used, GSE19617, to validate the hub genes. The verified hub genes' potential function was further explored using gene set enrichment analysis (GSEA). RESULTS: Through average link-level clustering, a total of seven modules were classified. A total of 938 hub genes were identified in the key module, and the key module's function mainly enriched was related to chemokine activities. Subsequently, four candidate genes, BTG3, CCR2, RAB10, and TMEM60, were filtered. The expression levels of these four hub genes were consistent in the GSE19617 and GSE33463 datasets. We plotted the ROC curve of the hub genes (all AUC > 0.70). Furthermore, the results of the GSEA for hub genes were correlated with complement and inflammatory responses. CONCLUSIONS: The hub genes (BTG3, CCR2, RAB10, and TMEM60) performed well in distinguishing the SSc-PAH patients from controls, and some biological functions, related to immunity, inflammation, and cytokines, might pave the way for follow-up studies on the diagnosis and treatment of SSc-PAH.
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The gene expression profiles of GSE33463 were obtained from the Gene Expression Omnibus (GEO) database. A free-scale gene coexpression network was constructed using the weighted gene coexpression network analysis (WGCNA) to explore the association between gene sets and clinical features and identify candidate biomarkers.
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The gene expression profiles of GSE33463 were obtained from the Gene Expression Omnibus (GEO) database. A free-scale gene coexpression network was constructed using the weighted gene coexpression network analysis (WGCNA) to explore the association between gene sets and clinical features and identify candidate biomarkers.
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The datasets analyzed during this study were publicly available databases, such as the Gene Expression Omnibus (GEO) dataset.
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Limited systemic sclerosis patients with PAH show biomarkers of inflammation and vascular injury
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The top 15 up-regulated genes and 15 down-regulated genes identified in the microarray dataset GSE33463.
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3.1. Differentially Expressed Genes between SSc-PAH and Normal Controls
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Table 1
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The top 15 up-regulated genes and 15 down-regulated genes identified in the microarray dataset GSE33463.
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Gene ontology enrichment analysis of turquoise module genes.
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3.4. Functional Annotation of the Key Module
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Gene ontology enrichment analysis of turquoise module genes.
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The gene expression profiles of GSE33463 were obtained from the Gene Expression Omnibus (GEO) database. A free-scale gene coexpression network was constructed using the weighted gene coexpression network analysis (WGCNA) to explore the association between gene sets and clinical features and identify candidate biomarkers.
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33680092", "kind": "science-record", "revision": 5, "content_hash": "sha256:baaa0a27474e764f93de3ebdad2f9eff3f18799321f918c1ec814a1a9201b16d", "created_at": "2026-11-01T15:41:27Z", "updated_at": "2026-11-01T22:03:15Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Candidate Genes Identified in Systemic Sclerosis-Related Pulmonary Arterial Hypertension Were Associated with Immunity, Inflammation, and Cytokines.", "doi": "10.1155/2021/6651009", "pmid": "33680092", "authors": ["Zhixiao Xu", "Jiaxing Ruan", "Lingyun Pan", "Chengshui Chen"], "journal": "Cardiovascular therapeutics", "year": 2021, "abstract": "BACKGROUND: Pulmonary complications of systemic sclerosis (SSc), including pulmonary arterial hypertension (PAH), are the leading causes of patient death. However, the precise molecular mechanisms of its etiology are unclear. This study's objective was to identify the candidate genes involved in the progression of SSc-PAH and investigate the genes' function.\nMETHODS: The gene expression profiles of GSE33463 were obtained from the Gene Expression Omnibus (GEO) database. A free-scale gene coexpression network was constructed using the weighted gene coexpression network analysis (WGCNA) to explore the association between gene sets and clinical features and identify candidate biomarkers. Then, gene ontology analysis was performed. A second dataset was used, GSE19617, to validate the hub genes. The verified hub genes' potential function was further explored using gene set enrichment analysis (GSEA).\nRESULTS: Through average link-level clustering, a total of seven modules were classified. A total of 938 hub genes were identified in the key module, and the key module's function mainly enriched was related to chemokine activities. Subsequently, four candidate genes, BTG3, CCR2, RAB10, and TMEM60, were filtered. The expression levels of these four hub genes were consistent in the GSE19617 and GSE33463 datasets. We plotted the ROC curve of the hub genes (all AUC > 0.70). Furthermore, the results of the GSEA for hub genes were correlated with complement and inflammatory responses.\nCONCLUSIONS: The hub genes (BTG3, CCR2, RAB10, and TMEM60) performed well in distinguishing the SSc-PAH patients from controls, and some biological functions, related to immunity, inflammation, and cytokines, might pave the way for follow-up studies on the diagnosis and treatment of SSc-PAH.", "claims": [{"id": "claim-method", "statement": "The gene expression profiles of GSE33463 were obtained from the Gene Expression Omnibus (GEO) database. 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