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pmid:40329965

Comprehensive analysis of lactylation-related gene and immune microenvironment in atrial fibrillation.

Yazhe Ma · Youcheng Wang · Yuanjia Ke · Qingyan Zhao · Jie Fan · Yang Chen

Frontiers in cardiovascular medicine · 2025 doi:10.3389/fcvm.2025.1567310

Paper

complete

Experiment

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Data

partial

Analysis

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title
Comprehensive analysis of lactylation-related gene and immune microenvironment in atrial fibrillation.
doi
10.3389/fcvm.2025.1567310
pmid
40329965
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[0]
Yazhe Ma
[1]
Youcheng Wang
[2]
Yuanjia Ke
[3]
Qingyan Zhao
[4]
Jie Fan
[5]
Yang Chen
journal
Frontiers in cardiovascular medicine
year
2025
abstract
Background: Atrial fibrillation (AF) is a common arrhythmia associated with an increased risk of stroke, heart failure, and mortality. Immune infiltration plays a crucial role in AF pathogenesis, yet its mechanisms remain unclear. Lactylation, a novel post-translational modification, has been implicated in immune regulation, but its association with AF remains unexplored. This study aims to elucidate the relationship between lactylation and immune infiltration in AF and identify potential diagnostic biomarkers. Methods: Gene expression data from left atrial tissue samples of AF and sinus rhythm (SR) patients were obtained from the Gene Expression Omnibus (GEO) database (GSE41177, GSE79768, GSE115574, GSE2240, GSE14975, and GSE128188). Differentially expressed genes (DEGs) between AF and SR samples were identified, followed by pathway enrichment and immune infiltration analysis. Correlation analysis and WGCNA were performed to assess interactions between lactylation-related genes and immune-associated DEGs. Machine learning models, including Random Forest and Support Vector Machine (SVM), were applied to select potential AF-related diagnostic biomarkers, and validated in the animal model (beagles; n = 6). Results: A total of 5,648 DEGs were identified, including six lactylation-related genes (DDX39A, ARID3A, TKT, NUP50, G6PD, and VCAN). Co-expression and WGCNA analyses identified lactylation- and immune-associated gene modules in AF. Functional enrichment analysis highlighted immune-related pathways such as T cell activation and neutrophil degranulation. A five-gene diagnostic model (FOXK1, JAM3, LOC100288798, MCM4, and RCAN1) achieved high predictive accuracy (AUC = 0.969 in training, 0.907 in self-test, and 0.950, 0.760, 0.890 in independent datasets). Experimental validation confirmed the upregulated expression of these biomarkers in AF. Conclusion: This study reveals a strong association between lactylation-related genes and immune infiltration in AF, suggesting their involvement in immune remodeling. The identified five-gene signature serves as a potential diagnostic biomarker set, offering novel insights into AF pathogenesis and contributing to improved diagnosis and targeted therapeutic strategies. Future studies integrating proteomic and single-cell analyses will further clarify the role of lactylation in AF.
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Machine learning models, including Random Forest and Support Vector Machine (SVM), were applied to select potential AF-related diagnostic biomarkers, and validated in the animal model (beagles; n = 6).
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Machine learning models, including Random Forest and Support Vector Machine (SVM), were applied to select potential AF-related diagnostic biomarkers, and validated in the animal model (beagles; n = 6).
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A five-gene diagnostic model (FOXK1, JAM3, LOC100288798, MCM4, and RCAN1) achieved high predictive accuracy (AUC = 0.969 in training, 0.907 in self-test, and 0.950, 0.760, 0.890 in independent datasets).
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A five-gene diagnostic model (FOXK1, JAM3, LOC100288798, MCM4, and RCAN1) achieved high predictive accuracy (AUC = 0.969 in training, 0.907 in self-test, and 0.950, 0.760, 0.890 in independent datasets).
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A five-gene diagnostic model (FOXK1, JAM3, LOC100288798, MCM4, and RCAN1) achieved high predictive accuracy (AUC = 0.969 in training, 0.907 in self-test, and 0.950, 0.760, 0.890 in independent datasets).
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A five-gene diagnostic model (FOXK1, JAM3, LOC100288798, MCM4, and RCAN1) achieved high predictive accuracy (AUC = 0.969 in training, 0.907 in self-test, and 0.950, 0.760, 0.890 in independent datasets).
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GSE41177
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GSE115574
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GSE2240
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GSE14975
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GSE128188
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The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.
basis
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quickly removed from the heart then perfumed qPCR. Statistical analysis Statistical analyses w
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Machine learning models, including Random Forest and Support Vector Machine (SVM), were applied to select potential AF-related diagnostic biomarkers, and validated in the animal model (beagles; n = 6).
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40329965", "kind": "science-record", "revision": 4, "content_hash": "sha256:efdae728384b30a3947de35b6c0e5e56c0216cf588a45cd31b236ca4c4e69d3b", "created_at": "2026-11-01T20:30:29Z", "updated_at": "2026-11-01T22:56:29Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comprehensive analysis of lactylation-related gene and immune microenvironment in atrial fibrillation.", "doi": "10.3389/fcvm.2025.1567310", "pmid": "40329965", "authors": ["Yazhe Ma", "Youcheng Wang", "Yuanjia Ke", "Qingyan Zhao", "Jie Fan", "Yang Chen"], "journal": "Frontiers in cardiovascular medicine", "year": 2025, "abstract": "Background: Atrial fibrillation (AF) is a common arrhythmia associated with an increased risk of stroke, heart failure, and mortality. Immune infiltration plays a crucial role in AF pathogenesis, yet its mechanisms remain unclear. Lactylation, a novel post-translational modification, has been implicated in immune regulation, but its association with AF remains unexplored. This study aims to elucidate the relationship between lactylation and immune infiltration in AF and identify potential diagnostic biomarkers.\nMethods: Gene expression data from left atrial tissue samples of AF and sinus rhythm (SR) patients were obtained from the Gene Expression Omnibus (GEO) database (GSE41177, GSE79768, GSE115574, GSE2240, GSE14975, and GSE128188). Differentially expressed genes (DEGs) between AF and SR samples were identified, followed by pathway enrichment and immune infiltration analysis. Correlation analysis and WGCNA were performed to assess interactions between lactylation-related genes and immune-associated DEGs. Machine learning models, including Random Forest and Support Vector Machine (SVM), were applied to select potential AF-related diagnostic biomarkers, and validated in the animal model (beagles; n = 6).\nResults: A total of 5,648 DEGs were identified, including six lactylation-related genes (DDX39A, ARID3A, TKT, NUP50, G6PD, and VCAN). Co-expression and WGCNA analyses identified lactylation- and immune-associated gene modules in AF. Functional enrichment analysis highlighted immune-related pathways such as T cell activation and neutrophil degranulation. A five-gene diagnostic model (FOXK1, JAM3, LOC100288798, MCM4, and RCAN1) achieved high predictive accuracy (AUC = 0.969 in training, 0.907 in self-test, and 0.950, 0.760, 0.890 in independent datasets). Experimental validation confirmed the upregulated expression of these biomarkers in AF.\nConclusion: This study reveals a strong association between lactylation-related genes and immune infiltration in AF, suggesting their involvement in immune remodeling. The identified five-gene signature serves as a potential diagnostic biomarker set, offering novel insights into AF pathogenesis and contributing to improved diagnosis and targeted therapeutic strategies. Future studies integrating proteomic and single-cell analyses will further clarify the role of lactylation in AF.", "claims": [{"id": "claim-method", "statement": "Machine learning models, including Random Forest and Support Vector Machine (SVM), were applied to select potential AF-related diagnostic biomarkers, and validated in the animal model (beagles; n = 6).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40329965", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Machine learning models, including Random Forest and Support Vector Machine (SVM), were applied to select potential AF-related diagnostic biomarkers, and validated in the animal model (beagles; n = 6)."}], "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:40329965", "locator": "sections[20] \"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 five-gene diagnostic model (FOXK1, JAM3, LOC100288798, MCM4, and RCAN1) achieved high predictive accuracy (AUC = 0.969 in training, 0.907 in self-test, and 0.950, 0.760, 0.890 in independent datasets).", "kind": "quantitative", "target": {"value": 0.969, "unit": "auc", "tolerance": null, "source": "A five-gene diagnostic model (FOXK1, JAM3, LOC100288798, MCM4, and RCAN1) achieved high predictive accuracy (AUC = 0.969 in training, 0.907 in self-test, and 0.950, 0.760, 0.890 in independent datasets)."}, "evidence": [{"asset": "source:pmid:40329965", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A five-gene diagnostic model (FOXK1, JAM3, LOC100288798, MCM4, and RCAN1) achieved high predictive accuracy (AUC = 0.969 in training, 0.907 in self-test, and 0.950, 0.760, 0.890 in independent datasets)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "A five-gene diagnostic model (FOXK1, JAM3, LOC100288798, MCM4, and RCAN1) achieved high predictive accuracy (AUC = 0.969 in training, 0.907 in self-test, and 0.950, 0.760, 0.890 in independent datasets).", "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:40329965"], "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:GSE115574"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:machine_learning_random_forest", "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:GSE115574"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:machine_learning_random_forest"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40329965", "role": "manuscript", "format": "xml", "media_type": "application/xml", 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