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pmid:41007695
Identification of Key Biomarkers Related to Lipid Metabolism in Acute Pancreatitis and Their Regulatory Mechanisms Based on Bioinformatics and Machine Learning.
Liang Zhang · Yujie Jiang · Taojun Jin · Mingxian Zheng · Yixuan Yap · Xuanyang Min · Jiayue Chen · Lin Yuan · Feng He · Bingduo Zhou
Biomedicines · 2025 doi:10.3390/biomedicines13092132
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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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This can trigger systemic inflammatory response syndrome and multi-organ dysfunction. Hyperlipidemia, mainly resulting from lipid metabolism disorders and elevated triglyceride levels, is a major etiological factor in AP. This study aims to investigate the role of lipid metabolism-related genes in the pathogenesis of AP and to propose novel strategies for its prevention and treatment. Methods: We obtained AP-related datasets GSE3644, GSE65146, and GSE121038 from the GEO database. Differentially expressed genes (DEGs) were identified using DEG analysis and gene set enrichment analysis (GSEA). To identify core lipid metabolism genes in AP, we performed least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination (SVM-RFE) analysis. Gene and protein interactions were predicted using GeneMANIA and AlphaFold. Finally, biomarker expression levels were quantified using Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) in an AP mouse model. Results: Seven lipid metabolism-related genes were identified as key biomarkers in AP: Amacr, Cyp39a1, Echs1, Gpd2, Osbpl9, Acsl4, and Mcee. The biological roles of these genes mainly involve fatty acid metabolism, cholesterol metabolism, lipid transport across cellular membranes, and mitochondrial function. Conclusions:Amacr, Cyp39a1, Echs1, Gpd2, Osbpl9, Acsl4, and Mcee are characteristic biomarkers of lipid metabolism abnormalities in AP. These findings are crucial for a deeper understanding of lipid metabolism pathways in AP and for the early implementation of preventive clinical measures, such as the control of blood lipid levels.", "claims": [{"id": "claim-method", "statement": "Differentially expressed genes (DEGs) were identified using the limma R package [21].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41007695", "locator": "sections[5] \"2.3. 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This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE121038"], "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:GSE121038"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41007695", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3390/biomedicines13092132", "sha256": 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(GSEA, http://www.gsea-msigdb.org/, accessed on 6 December 2024), Gene Ontology (GO, https://geneontology.org/, accessed on 24 December 2024), and Kyoto Encyclopedia of Genes and Genomes (KEGG, https://www.genome.jp/kegg/, accessed on 24 December 2024), and further inquiries can be directed to the corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3424897", "GSM3424898", "GSM3424899", "GSM3424900", "GSM3424901", "GSM3424902", "GSM3424903", "GSM3424904", "GSM3424905", "GSM3424906", "GSM3424907", "GSM3424908", "GSM3424909", "GSM3424910", "GSM3424911"], "sample_count": 15, "group_sizes": null, "group_sizes_basis": null, "platform": "10787", "taxon": "Mus musculus", "title": "The protective effect of betacellulin against acute pancreatitis is ERBB4-dependent", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, 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to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets generated and/or analyzed during this study are available at Gene Expression Omnibus datasets (GEO, https://www.ncbi.nlm.nih.gov/geo/, accessed on 9 October 2024 GSE3644, GSE65146, GSE121038) and https://www.gsea-msigdb.org/gsea/index.jsp, accessed on 16 November 2024, were obtained and analyzed in Gene Set Enrichment Analysis (GSEA, http://www.gsea-msigdb.org/, accessed on 6 December 2024), Gene Ontology (GO, https://geneontology.org/, accessed on 24 December 2024), and Kyoto Encyclopedia of Genes and Genomes (KEGG, https://www.genome.jp/kegg/, accessed on 24 December 2024), and further inquiries can be directed to the corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM631755", "GSM631756", "GSM631757", "GSM631758", "GSM631759", "GSM631760", "GSM631761", "GSM631762", "GSM631763", 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https://geneontology.org/, accessed on 24 December 2024), and Kyoto Encyclopedia of Genes and Genomes (KEGG, https://www.genome.jp/kegg/, accessed on 24 December 2024), and further inquiries can be directed to the corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM84549", "GSM84550", "GSM84551", "GSM84552", "GSM84553", "GSM84554", "GSM84555", "GSM84556", "GSM84557", "GSM84558", "GSM84559", "GSM84560"], "sample_count": 12, "group_sizes": null, "group_sizes_basis": null, "platform": "339", "taxon": "Mus musculus", "title": "Effects of caerulein on Mist1KO pancreas", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE65146", "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=GSE65146", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE65146", "version": null, "note": "The datasets generated and/or analyzed during this study are available at Gene Expression Omnibus datasets (GEO, https://www.ncbi.nlm.nih.gov/geo/, accessed on 9 October 2024 GSE3644, GSE65146, GSE121038) and https://www.gsea-msigdb.org/gsea/index.jsp, accessed on 16 November 2024, were obtained and analyzed in Gene Set Enrichment Analysis (GSEA, http://www.gsea-msigdb.org/, accessed on 6 December 2024), Gene Ontology (GO, https://geneontology.org/, accessed on 24 December 2024), and Kyoto Encyclopedia of Genes and Genomes (KEGG, https://www.genome.jp/kegg/, accessed on 24 December 2024), and further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets generated and/or analyzed during this study are available at Gene Expression Omnibus datasets (GEO, https://www.ncbi.nlm.nih.gov/geo/, accessed on 9 October 2024 GSE3644, GSE65146, GSE121038) and https://www.gsea-msigdb.org/gsea/index.jsp, accessed on 16 November 2024, were obtained and analyzed in Gene Set Enrichment Analysis (GSEA, http://www.gsea-msigdb.org/, accessed on 6 December 2024), Gene Ontology (GO, https://geneontology.org/, accessed on 24 December 2024), and Kyoto Encyclopedia of Genes and Genomes (KEGG, https://www.genome.jp/kegg/, accessed on 24 December 2024), and further inquiries can be directed to the corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1588057", "GSM1588058", "GSM1588059", "GSM1588060", "GSM1588061", "GSM1588062", "GSM1588063", "GSM1588064", "GSM1588065", "GSM1588066", "GSM1588067", "GSM1588068", "GSM1588069", "GSM1588070", "GSM1588071", "GSM1588072", "GSM1588073", "GSM1588074", "GSM1588075", "GSM1588076", "GSM1588077", "GSM1588078", 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on 24 December 2024), and Kyoto Encyclopedia of Genes and Genomes (KEGG, https://www.genome.jp/kegg/, accessed on 24 December 2024), and further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets generated and/or analyzed during this study are available at Gene Expression Omnibus datasets (GEO, https://www.ncbi.nlm.nih.gov/geo/, accessed on 9 October 2024 GSE3644, GSE65146, GSE121038) and https://www.gsea-msigdb.org/gsea/index.jsp, accessed on 16 November 2024, were obtained and analyzed in Gene Set Enrichment Analysis (GSEA, http://www.gsea-msigdb.org/, accessed on 6 December 2024), Gene Ontology (GO, https://geneontology.org/, accessed on 24 December 2024), and Kyoto Encyclopedia of Genes and Genomes (KEGG, https://www.genome.jp/kegg/, accessed on 24 December 2024), and further inquiries can be directed to the corresponding author.", "access_statement_kind": 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"group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Affymetrix profiling of IMIDIA biobank samples from organ donors and partially pancreatectomized patients", "resolution_checked_at": "2026-11-01T18:06:44Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE121038 not downloaded", "asset:data:geo:GSE121038 licence not read", "asset:data:geo:GSE25724 not downloaded", "asset:data:geo:GSE25724 licence not read", "asset:data:geo:GSE3644 not downloaded", "asset:data:geo:GSE3644 licence not read", "asset:data:geo:GSE65146 not downloaded", "asset:data:geo:GSE65146 licence not read", "asset:data:geo:GSE76896 not downloaded", "asset:data:geo:GSE76896 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": 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"tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE3644", "GSE65146", "GSE121038", "GSE25724", "GSE76896"], "resolved_accessions": ["GSE3644", "GSE65146", "GSE121038", "GSE25724", "GSE76896"], "statements": ["The datasets generated and/or analyzed during this study are available at Gene Expression Omnibus datasets (GEO, https://www.ncbi.nlm.nih.gov/geo/, accessed on 9 October 2024 GSE3644, GSE65146, GSE121038) and https://www.gsea-msigdb.org/gsea/index.jsp, accessed on 16 November 2024, were obtained and analyzed in Gene Set Enrichment Analysis (GSEA, http://www.gsea-msigdb.org/, accessed on 6 December 2024), Gene Ontology (GO, https://geneontology.org/, accessed on 24 December 2024), and Kyoto Encyclopedia of Genes and Genomes (KEGG, https://www.genome.jp/kegg/, accessed on 24 December 2024), and further inquiries can be directed to the corresponding author."], "basis": "The paper names GSE3644, GSE65146, GSE121038, GSE25724, GSE76896 in Gene Expression Omnibus database (GEO) and the accession resolves in the repository. 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