{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T03:31:24Z","timestamp":1783395084286,"version":"3.54.6"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Aortic dissection, particularly acute type A aortic dissection (ATAAD), is a life-threatening cardiovascular emergency with alarmingly high mortality rates globally. Despite advancements in imaging techniques like computed tomography angiography (CTA), delayed diagnosis and incomplete understanding of molecular mechanisms persist, contributing to poor outcomes. Recent studies highlight the role of immune dysregulation, vascular smooth muscle cell (VSMC) apoptosis, and metabolic-epigenetic interactions in AD pathogenesis, underscoring the need for novel biomarkers and therapeutic targets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aims to identify critical genes and molecular pathways associated with ATAAD, develop a multi-omics diagnostic model, and evaluate potential therapeutic interventions to improve clinical outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Transcriptome datasets from the Gene Expression Omnibus (GEO) database were analyzed using differential expression analysis, weighted gene co-expression network analysis (WGCNA), and machine learning algorithms (SVM, Random Forest, LASSO regression). Functional enrichment and immunoinfiltration analyses were performed to explore biological pathways and immune cell interactions. External dataset validation and PCR testing of clinical samples (n = 9) were conducted to confirm gene expression differences. A nomogram diagnostic model was constructed and evaluated for predictive accuracy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Six core genes were identified: <jats:italic>Ccl2<\/jats:italic>, <jats:italic>Cdh8<\/jats:italic>, <jats:italic>Hk2<\/jats:italic>, <jats:italic>Tph1<\/jats:italic>, <jats:italic>Npy1r<\/jats:italic>, and <jats:italic>Slc24a4<\/jats:italic>, with four (<jats:italic>Ccl2<\/jats:italic>, <jats:italic>Hk2<\/jats:italic>, <jats:italic>Tph1<\/jats:italic>, and <jats:italic>Npy1r<\/jats:italic>) showing significant differential expression in clinical validation. Functional enrichment revealed associations with immune cell migration, vascular development regulation, extracellular matrix pathways, and the PI3K-Akt signaling pathway. Immunoinfiltration analysis demonstrated increased infiltration of B cell precursors, resting NK cells, and M2 macrophages in ATAAD tissues, negatively correlating with core gene expression. The nomogram model exhibited high diagnostic precision (AUC=0.935, 95% CI: 0.908\u20130.963), supported by calibration and decision curve analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study identifies key molecular markers and pathways in ATAAD pathogenesis, emphasizing the role of immune dysregulation and extracellular matrix remodeling. The multi-omics diagnostic model provides a novel tool for early screening, potentially reducing mortality through timely intervention. These findings advance the understanding of aortic dissection mechanisms and offer actionable targets for future research and clinical applications.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fgene.2025.1586880","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T05:25:45Z","timestamp":1745472345000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Key gene screening and diagnostic model establishment for acute type a aortic dissection"],"prefix":"10.3389","volume":"16","author":[{"given":"Yue","family":"Pan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiming","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuesong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weizhang","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1016\/j.tcb.2022.02.003","article-title":"Regulation of gene expression by glycolytic and gluconeogenic enzymes","volume":"32","author":"Bian","year":"2022","journal-title":"Trends Cell Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"3652","DOI":"10.1073\/pnas.91.9.3652","article-title":"Monocyte chemoattractant protein 1 acts as a T-lymphocyte chemoattractant","volume":"91","author":"Carr","year":"1994","journal-title":"Proc. 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