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pmid:34790731

Weighted gene co-expression network analysis reveals specific modules and hub genes related to immune infiltration of osteoarthritis.

Jiangang Cao · Han Ding · Jun Shang · Lei Ma · Qi Wang · Shiqing Feng

Annals of translational medicine · 2021 doi:10.21037/atm-21-4566

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complete

Experiment

complete

Data

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Analysis

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title
Weighted gene co-expression network analysis reveals specific modules and hub genes related to immune infiltration of osteoarthritis.
doi
10.21037/atm-21-4566
pmid
34790731
authors array · 6 items
[0]
Jiangang Cao
[1]
Han Ding
[2]
Jun Shang
[3]
Lei Ma
[4]
Qi Wang
[5]
Shiqing Feng
journal
Annals of translational medicine
year
2021
abstract
BACKGROUND: The incidence of osteoarthritis (OA), a chronic degenerative disease, is increasing every year. There is no effective clinical treatment for OA and the pathological mechanism remains unclear. Early diagnosis is an effective strategy to control the progress of OA. In this study, we aimed to identify potential early diagnostic biomarkers. METHODS: We downloaded the gene expression profile dataset, GSE51588 and GSE55235, from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) public database. The differentially expressed genes (DEGs) were screened out using the "limma" R package. Weighted gene co-expression network analysis (WGCNA) was utilized to build the co-expression network between the normal and OA samples. A Venn diagram was constructed to detect the hub genes. Potential molecular mechanisms and signaling pathways were enriched by gene set variation analysis (GSVA). Single sample gene set enrichment analysis (ssGSEA) was used to identify the immune infiltration of OA. RESULTS: We screened out three hub genes based on WGCNA and DEGs in this study. GSVA results showed that nuclear factor interleukin-3 (NFIL3) was related to tumor necrosis factor alpha (TNF-α) signaling via nuclear factor kappa-B (NF-κB), the reactive oxygen species pathway, and myelocytomatosis (MYC) targets v2. Highly-expressed ADM (adrenomedullin) pathways included TNF-α signaling via NF-κB, the reactive oxygen species pathway, and ultraviolet (UV) response up. OGN (osteoglycin)-enriched pathways included epithelial mesenchymal transition, coagulation, and peroxisome. CONCLUSIONS: We identified three hub genes (NFIL3, ADM, and OGN) that were correlated to the development and progression of OA, which may provide new biomarkers for early diagnosis.
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The differentially expressed genes (DEGs) were screened out using the “limma” R package.
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The series matrix file, GSE51588, was downloaded from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) public database (20). There were 40 groups of human OA data (including 20 LT groups and 20 MT groups) and 10 groups of human non-OA data (including five LT groups and five MT groups) for the WGCNA co-expression network construction.
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The results showed that the AUC values of the three core genes were greater than 0.8 (NFIL3: AUC =0.957; ADM: AUC =0.900; OGN: AUC =0.815), indicating that these three hub genes could be effective indicators for clear diagnosis (Figure 3B-3D).
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Genome-wide Expression Profiles of Subchondral Bone in Osteoarthritis
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34790731", "kind": "science-record", "revision": 5, "content_hash": "sha256:1856e0c8e776f0f05af2bef3c59cc116201fe6ef90f152a55fc12dc728906747", "created_at": "2026-11-01T17:36:29Z", "updated_at": "2026-11-01T22:47:54Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Weighted gene co-expression network analysis reveals specific modules and hub genes related to immune infiltration of osteoarthritis.", "doi": "10.21037/atm-21-4566", "pmid": "34790731", "authors": ["Jiangang Cao", "Han Ding", "Jun Shang", "Lei Ma", "Qi Wang", "Shiqing Feng"], "journal": "Annals of translational medicine", "year": 2021, "abstract": "BACKGROUND: The incidence of osteoarthritis (OA), a chronic degenerative disease, is increasing every year. There is no effective clinical treatment for OA and the pathological mechanism remains unclear. Early diagnosis is an effective strategy to control the progress of OA. In this study, we aimed to identify potential early diagnostic biomarkers.\nMETHODS: We downloaded the gene expression profile dataset, GSE51588 and GSE55235, from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) public database. The differentially expressed genes (DEGs) were screened out using the \"limma\" R package. Weighted gene co-expression network analysis (WGCNA) was utilized to build the co-expression network between the normal and OA samples. A Venn diagram was constructed to detect the hub genes. Potential molecular mechanisms and signaling pathways were enriched by gene set variation analysis (GSVA). Single sample gene set enrichment analysis (ssGSEA) was used to identify the immune infiltration of OA.\nRESULTS: We screened out three hub genes based on WGCNA and DEGs in this study. GSVA results showed that nuclear factor interleukin-3 (NFIL3) was related to tumor necrosis factor alpha (TNF-α) signaling via nuclear factor kappa-B (NF-κB), the reactive oxygen species pathway, and myelocytomatosis (MYC) targets v2. Highly-expressed ADM (adrenomedullin) pathways included TNF-α signaling via NF-κB, the reactive oxygen species pathway, and ultraviolet (UV) response up. OGN (osteoglycin)-enriched pathways included epithelial mesenchymal transition, coagulation, and peroxisome.\nCONCLUSIONS: We identified three hub genes (NFIL3, ADM, and OGN) that were correlated to the development and progression of OA, which may provide new biomarkers for early diagnosis.", "claims": [{"id": "claim-method", "statement": "The differentially expressed genes (DEGs) were screened out using the “limma” R package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34790731", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "The differentially expressed genes (DEGs) were screened out using the “limma” R package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The series matrix file, GSE51588, was downloaded from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) public database (20). There were 40 groups of human OA data (including 20 LT groups and 20 MT groups) and 10 groups of human non-OA data (including five LT groups and five MT groups) for the WGCNA co-expression network construction.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34790731", "locator": "sections[3] \"Microarray data sources and processing\" paragraph 2", "quote": "The series matrix file, GSE51588, was downloaded from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) public database (20). There were 40 groups of human OA data (including 20 LT groups and 20 MT groups) and 10 groups of human non-OA data (including five LT groups and five MT groups) for the WGCNA co-expression network construction."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The three hub genes had diagnostic AUC values of 0.957 for NFIL3, 0.900 for ADM, and 0.815 for OGN.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34790731", "locator": "sections[12] \"Identification of hub genes and diagnostic efficacy verification\" paragraph 2", "quote": "The results showed that the AUC values of the three core genes were greater than 0.8 (NFIL3: AUC =0.957; ADM: AUC =0.900; OGN: AUC =0.815), indicating that these three hub genes could be effective indicators for clear diagnosis (Figure 3B-3D)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The three hub genes had diagnostic AUC values of 0.957 for NFIL3, 0.900 for ADM, and 0.815 for OGN.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:34790731"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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