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pmid:37082197
Identification and characterization of bone/cartilage-associated signatures in common fibrotic skin diseases.
Ting Wu · Yifan Jin · Fangqi Chen · Xiuyun Xuan · Juanmei Cao · Yan Liang · Yuqing Wang · Jinshan Zhan · Mengjie Zhao · Changzheng Huang
Frontiers in genetics · 2023 doi:10.3389/fgene.2023.1121728
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Complete file
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However, effective treatments of fibrotic skin diseases remain limited, and their pathological mechanisms require further investigation. This study aims to investigate the common biomarkers and therapeutic targets in two major fibrotic skin diseases, namely, keloid and systemic sclerosis (SSc), by bioinformatics analysis. Methods: The keloid (GSE92566) and SSc (GSE95065) datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified, followed by functional enrichment analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We then constructed a protein-protein interaction (PPI) network for the identification of hub genes. We explored the possibility of further functional enrichment analysis of hub genes on the Metascape, GeneMANIA, and TissueNexus platforms. Transcription factor (TF)-hub gene and miRNA-hub gene networks were established using NetworkAnalyst. We fixed GSE90051 and GSE76855 as the external validation datasets. Student's t-test and receiver operating characteristic (ROC) curve were used for candidate hub gene validation. Hub gene expression was assessed in vitro by quantitative real-time PCR. Results: A total of 157 overlapping DEGs (ODEGs) were retrieved from the GSE92566 and GSE95065 datasets, and five hub genes (COL11A1, COL5A2, ASPN, COL10A1, and COMP) were identified and validated. Functional studies revealed that hub genes were predominantly enriched in bone/cartilage-related and collagen-related processes. FOXC1 and miR-335-5p were predicted to be master regulators at both transcriptional and post-transcriptional levels. Conclusion: COL11A1, COL5A2, ASPN, COL10A1, and COMP may help understand the pathological mechanism of the major fibrotic skin diseases; moreover, FOXC1 and miR-355-5p could build a regulatory network in keloid and SSc.", "claims": [{"id": "claim-method", "statement": "The expression of the hub genes in keloid, SSc, and normal tissues was validated using Student’s t‐test in GraphPad Prism 8.0.1, and their specificity and sensitivity were further evaluated by the receiver operating characteristic curve analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37082197", "locator": "sections[10] \"Validation of the performance of hub genes\" paragraph 2", "quote": "The expression of the hub genes in keloid, SSc, and normal tissues was validated using Student’s t‐test in GraphPad Prism 8.0.1, and their specificity and sensitivity were further evaluated by the receiver operating characteristic curve analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material; further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37082197", "locator": "sections[21] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material; further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of 157 overlapping DEGs (ODEGs) were retrieved from the GSE92566 and GSE95065 datasets, and five hub genes (COL11A1, COL5A2, ASPN, COL10A1, and COMP) were identified and validated.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37082197", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A total of 157 overlapping DEGs (ODEGs) were retrieved from the GSE92566 and GSE95065 datasets, and five hub genes (COL11A1, COL5A2, ASPN, COL10A1, and COMP) were identified and validated."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "A total of 157 overlapping DEGs (ODEGs) were retrieved from the GSE92566 and GSE95065 datasets, and five hub genes (COL11A1, COL5A2, ASPN, COL10A1, and COMP) were identified and validated.", "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:37082197"], "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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