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pmid:40823351
Bioinformatics Analysis and Identification of Ferroptosis-Related Gene TIMP1 as a Potential Biomarker of Asthma.
Yingjie Guo · He Zhu · Jiahui Lei · Fan Gao · Jinxin Ma · Limin Zhao
Journal of inflammation research · 2025 doi:10.2147/JIR.S529209
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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Studies have shown that ferroptosis may play a crucial role in the pathogenesis of asthma. However, ferroptosis-related genes have not yet been identified in the airway epithelial cells of patients with asthma. This study aims to identify ferroptosis-related genes in asthmatic airway epithelial cells, providing potential therapeutic targets for management of asthma.\nMethods: We obtained the asthma dataset GSE63142 from the GEO database and the ferroptosis genes from the FerrDb database. Key co-expression modules and core genes were identified through Weighted Gene Co-expression Network Analysis (WGCNA), followed by functional enrichment analyses on the core genes. By overlapping the core genes with ferroptosis-related genes, we identified a hub gene, Tissue Inhibitor of Metalloproteinase 1 (TIMP1). It was validated using an independent dataset GSE43696 and clinical samples. Gene Set Enrichment Analysis (GSEA) was performed to further explore its biological relevance.\nResults: WGCNA analysis yielded 23 core genes. Functional enrichment analysis revealed that these genes were significantly enriched in metabolic processes and ferroptosis. TIMP1 was identified as the sole hub gene. The expression of TIMP1 was significantly elevated in the SA groups compared to both the MMA groups (P<0.05) and normal controls (P<0.0001).The AUC values for diagnosing MMA and SA were 0.713 and 0.865, respectively. GSEA results indicated that TIMP1 was primarily enriched in the HIF-1 signaling pathway. TIMP1 mRNA expression levels were significantly higher in asthmatic groups compared to non-asthmatic control groups (P<0.05), while TIMP1 protein expression levels were markedly higher in asthmatic groups (P<0.001).\nConclusion: Our findings suggest that TIMP1 is associated with ferroptosis in asthma and may serve as a novel biomarker or therapeutic target.", "claims": [{"id": "claim-method", "statement": "Key co-expression modules and core genes were identified through Weighted Gene Co-expression Network Analysis (WGCNA), followed by functional enrichment analyses on the core genes.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40823351", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Key co-expression modules and core genes were identified through Weighted Gene Co-expression Network Analysis (WGCNA), followed by functional enrichment analyses on the core genes."}], "state": "complete"}, {"id": "claim-data-access", "statement": "We provide details of the materials and methods in our manuscript.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40823351", "locator": "sections[26] \"Data Sharing Statement\" paragraph 2", "quote": "We provide details of the materials and methods in our manuscript."}], "state": "complete"}, {"id": "claim-target-result", "statement": "TIMP1 was identified as the sole hub gene.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40823351", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "TIMP1 was identified as the sole hub gene."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "TIMP1 was identified as the sole hub gene.", "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:40823351"], "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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