EDN1 and NTF3 in keloid pathogenesis: computational and experimental evidence as novel diagnostic biomarkers for fibrosis and inflammation.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40051702", "kind": "science-record", "revision": 4, "content_hash": "sha256:068e442412b0982e2b4ea4c457a7cf40dec8497553aba044b5acb2b3412ecaeb", "created_at": "2026-11-01T20:30:15Z", "updated_at": "2026-11-01T22:56:11Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "EDN1 and NTF3 in keloid pathogenesis: computational and experimental evidence as novel diagnostic biomarkers for fibrosis and inflammation.", "doi": "10.3389/fgene.2025.1516451", "pmid": "40051702", "authors": ["Hui Gong", "Jing Liu", "Nanji Chen", "Hengguang Zhao", "Bailin He", "Hongpei Zhang", "Wenping Wang", "Yi Tian"], "journal": "Frontiers in genetics", "year": 2025, "abstract": "Objective: To investigate the roles of oxidative stress-related differentially expressed genes (OSRDEGs) in keloid formation and explore their potential value in diagnosis and treatment.\nMethods: Gene expression data from the GEO database, including GSE145725 and GSE44270 as training sets and GSE7890 as a validation set, were utilized. OSRDEGs were identified, followed by Weighted Gene Co-expression Network Analysis (WGCNA), GO/KEGG enrichment analysis, and Gene Set Enrichment Analysis (GSEA). Key genes were further screened through protein-protein interaction (PPI) network analysis and receiver operating characteristic (ROC) curve analysis. miRNA targets, transcription factors (TF), and potential drug targets of these genes were predicted. Immune cell infiltration analysis was performed to assess the association between OSRDEGs and immune cells, which was validated using GSE7890. Finally, the expression of key genes was experimentally validated using quantitative PCR (qPCR), immunohistochemistry (IHC), and hematoxylin-eosin (HE) staining.\nResults: A total of 13 OSRDEGs were identified. WGCNA and functional enrichment analyses revealed that these genes were primarily involved in fibrosis and inflammatory processes in keloids, such as the MAPK signaling pathway, lymphocyte and monocyte proliferation, and inflammatory pathways involving IL-18 and IL-23. PPI network analysis, ROC analysis, and immune infiltration results identified Endothelin-1 (EDN1) and Neurotrophin-3(NTF3) as key genes with high sensitivity and specificity. These genes were positively and negatively correlated with activated mast cells, respectively, suggesting their dual regulatory roles in fibrosis and inflammation. External dataset validation, qPCR, correlation analysis, HE staining, and IHC results demonstrated that EDN1 and NTF3 were highly expressed in keloid tissues and were associated with excessive collagen deposition and immune cell infiltration.\nConclusion: EDN1 and NTF3, as OSRDEGs, play critical roles in the pathogenesis and progression of keloids. They may contribute to fibrosis and inflammation through the regulation of oxidative stress, the MAPK signaling pathway, and mast cell activation. These findings highlight EDN1 and NTF3 as potential diagnostic biomarkers and therapeutic targets, providing novel insights into the pathogenesis and treatment strategies for keloids.", "claims": [{"id": "claim-method", "statement": "Gene expression differences between groups were evaluated using t-tests for two-group comparisons, while one-way ANOVA was applied for comparisons across multiple groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40051702", "locator": "sections[15] \"2.8 Statistical analysis\" paragraph 2", "quote": "Gene expression differences between groups were evaluated using t-tests for two-group comparisons, while one-way ANOVA was applied for comparisons across multiple groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data presented in the study are deposited in the GEO repository under accession numbers GSE145725, GSE44270, and GSE7890.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40051702", "locator": "sections[40] \"Data availability statement\" paragraph 2", "quote": "The data presented in the study are deposited in the GEO repository under accession numbers GSE145725, GSE44270, and GSE7890."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of 13 OSRDEGs were identified.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40051702", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A total of 13 OSRDEGs were identified."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A total of 13 OSRDEGs were identified.", "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:40051702"], "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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External dataset validation, qPCR, correlation analysis, HE staining, and IHC", "colors representing changes in logFC. 3.7.1 qPCR analysis of NTF3 and EDN1 in normal skin and", "nd EDN1 in normal skin and keloid tissue The qPCR analysis of NTF3 and EDN1 mRNA expression le"], "order_basis": "paper_text_order:1079", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["lly validated using quantitative PCR (qPCR), immunohistochemistry (IHC), and hematoxylin-eosin (HE) staining.", "antitative PCR (qPCR), immunohistochemistry (IHC), and hematoxylin-eosin (HE) staining. 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