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As neutrophils are the first innate immune responders mobilized following infarction, we employed an integrated multi-omics and machine learning approach to identify neutrophil-driven molecular signatures with diagnostic potential. By analyzing multiple peripheral blood transcriptomic datasets, we conducted differential expression and immune infiltration analyses, followed by machine learning-based feature selection to pinpoint key genes linked to neutrophil activity. Integration of these findings with single-cell transcriptomic data further clarified the neutrophil-specific expression patterns of candidate genes during AMI progression. Using a joint diagnostic model, we identified MCEMP1, NFE2, and AQP9 as the most informative predictors, with MCEMP1 emerging as the primary contributor. Experimental validation in a murine model of myocardial infarction (MI) confirmed rapid upregulation of MCEMP1 after injury, closely mirroring the kinetics of neutrophil infiltration. Collectively, these findings delineate a neutrophil-associated molecular profile of early AMI and highlight MCEMP1 as a promising noninvasive biomarker and a potential therapeutic target for modulating neutrophil-driven myocardial injury.<\/jats:p>","DOI":"10.3390\/biology15100781","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T13:12:08Z","timestamp":1779455528000},"page":"781","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Uncovering Potential Neutrophil-Related Biomarkers for Early AMI Diagnosis"],"prefix":"10.3390","volume":"15","author":[{"given":"Yuwei","family":"Liu","sequence":"first","affiliation":[{"name":"School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucheng","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diru","family":"Yao","sequence":"additional","affiliation":[{"name":"Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebenezeri Erasto","family":"Ngowi","sequence":"additional","affiliation":[{"name":"Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China"},{"name":"Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2473-5891","authenticated-orcid":false,"given":"Moussa","family":"Omorou","sequence":"additional","affiliation":[{"name":"Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China"},{"name":"Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7745-4946","authenticated-orcid":false,"given":"Ning","family":"Hou","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weibo","family":"Dai","sequence":"additional","affiliation":[{"name":"Pharmacology Laboratory, Zhongshan Hospital of Traditional Chinese Medicine, Affiliated with Guangzhou University of Traditional Chinese Medicine, Zhongshan 528400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longlong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine of Integrated Traditional Chinese and Western Medicine, The Affiliated International Zhuang Medicine Hospital of Guangxi University of Chinese Medicine, Nanning 530200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guihua","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine of Integrated Traditional Chinese and Western Medicine, The Affiliated International Zhuang Medicine Hospital of Guangxi University of Chinese Medicine, Nanning 530200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7545-3395","authenticated-orcid":false,"given":"Aijun","family":"Qiao","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China"},{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550004, China"},{"name":"School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China"},{"name":"Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China"},{"name":"Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.5334\/gh.1288","article-title":"The Heart of the World","volume":"19","author":"Perel","year":"2024","journal-title":"Glob. 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