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pmid:40642530
Identification of diagnostic hub genes related to energy metabolism in idiopathic pulmonary fibrosis.
S Zhao · B C Sun · N Liu · R Huo · L S Liu · J P Wang · C Y Fang
Frontiers in molecular biosciences · 2025 doi:10.3389/fmolb.2025.1596364
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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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Emerging evidence implicates dysregulated energy metabolism in driving fibroblast activation and extracellular matrix remodeling during IPF pathogenesis. To systematically investigate metabolic reprogramming mechanisms, we performed integrated bioinformatics analyses focusing on energy metabolism-related differentially expressed genes (EMRDEGs) and their regulatory networks in fibrotic remodeling.\nMethods: Differentially Expressed Genes (DEGs) were identified by accessing datasets GSE242063 and GSE110147 from the GEO database. Energy metabolism-related genes (EMRGs) were extracted from GeneCards, followed by Venn diagram analysis to obtain EMRDEGs. Subsequent analyses included functional enrichment (GO/KEGG), protein-protein interaction network, and mRNA-miRNA, mRNA-transcription factor interaction networks. Immune infiltration analyses, including the CIBERSORT algorithm, and single-sample gene set enrichment analysis (ssGSEA), were subsequently conducted.\nResults: We identified 12 EMRDEGs and eight hub genes (ACSL1, CEBPD, CFH, HMGCS1, IL6, SOCS3, TLR2, and UCP2). Regulatory network analysis revealed HMGCS1 as a novel IPF-associated gene interacting with PPARα signaling, while SOCS3 coordinated multiple hub genes (IL6, CEBPD, UCP2, and CFH) through FOXA1/2-mediated transcriptional regulation alongside JAK/STAT3 pathway suppression. Immune profiling demonstrated significant hub gene-immune cell correlations, particularly neutrophil-mediated differential gene expression and microenvironment remodeling.\nConclusion: The core EMRDEGs (HMGCS1 and SOCS3) and prioritized pathways (PPARα signaling, FOXA networks, JAK/STAT3 suppression) elucidate metabolic reprogramming mechanisms in fibrotic progression. These molecular signatures provide novel clinical biomarkers for IPF diagnosis.", "claims": [{"id": "claim-method", "statement": "To identify potential diagnostic and therapeutic targets and pathways of differentially expressed genes (DEGs) in Idiopathic Pulmonary Fibrosis (IPF), we utilized the limma package (Version 3.58.1) (Ritchie et al., 2015) for the analysis of IPF datasets (GSE24206 and GSE110147).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40642530", "locator": "sections[4] \"2.2 Identification of differentially expressed genes related to energy metabolism\" paragraph 3", "quote": "To identify potential diagnostic and therapeutic targets and pathways of differentially expressed genes (DEGs) in Idiopathic Pulmonary Fibrosis (IPF), we utilized the limma package (Version 3.58.1) (Ritchie et al., 2015) for the analysis of IPF datasets (GSE24206 and GSE110147)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40642530", "locator": "sections[23] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "We identified 12 EMRDEGs and eight hub genes (ACSL1, CEBPD, CFH, HMGCS1, IL6, SOCS3, TLR2, and UCP2).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40642530", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We identified 12 EMRDEGs and eight hub genes (ACSL1, CEBPD, CFH, HMGCS1, IL6, SOCS3, TLR2, and UCP2)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "We identified 12 EMRDEGs and eight hub genes (ACSL1, CEBPD, CFH, HMGCS1, IL6, SOCS3, TLR2, and UCP2).", "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:40642530"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE110147"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE110147"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40642530", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fmolb.2025.1596364", "sha256": "sha256:bff57b88bde98b2f940f1a98a8c30fd7654869f6581d60e3b62d436921675705", "bytes": 64877, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fmolb.2025.1596364", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12241802", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE110147", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE110147", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE110147", "version": null, "note": "The datasets presented in this study can be found in online repositories. 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