{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:16:26Z","timestamp":1758586586317,"version":"3.44.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"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. Med."],"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>To explore the changes in differentially expressed genes in pericoronary adipose tissue (PCAT) and serum from patients with coronary artery disease (CAD) complicated with type 2 diabetes mellitus (T2DM) and to analyse its correlation with PCAT radiomic features based on coronary CT angiography (CCTA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Intersecting genes that were differentially expressed in both CAD and T2DM patients were obtained from the GEO database and analyzed to obtain candidate genes. PCAT and serum samples were collected from CAD patients who underwent coronary artery bypass grafting (CABG) from May 2023 to January 2024. RT\u2013qPCR was used to determine the expression of candidate differentially expressed genes in PCAT, to search for genes related to patients with CAD combined with T2DM, and to verify the protein expression levels by immunohistochemistry (IHC). Enzyme-linked immunosorbent assays (ELISAs) were also used to determine the expression of candidate differentially expressed genes in the serum. Finally, the PCAT radiomic features of the right coronary artery in patients with CAD combined with T2DM were extracted and correlated with the candidate genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>HLA-DRB1<\/jats:italic>, <jats:italic>TP53<\/jats:italic>, and <jats:italic>CCR9<\/jats:italic> were screened from the GEO database. RT\u2013qPCR results revealed that <jats:italic>TP53<\/jats:italic> expression was significantly increased in the T2DM group compared with the control group (3.082\u202f\u00b1\u202f0.580 vs. 1.663\u202f\u00b1\u202f0.698, <jats:italic>p<\/jats:italic> &amp;lt;\u202f0.001). IHC results revealed that the area of positive expression around the nucleus was increased in the fat cells of the T2DM group compared with those of the control group, with increased perinuclear areas with positive expression (0.521\u202f\u00b1\u202f0.082 vs. 0.327\u202f\u00b1\u202f0.074, <jats:italic>p<\/jats:italic> &amp;lt;\u202f0.001), and 14 PCAT radiomic features in CAD combined with T2DM patients correlated with <jats:italic>TP53<\/jats:italic> (r<jats:sub>s<\/jats:sub>\u202f&amp;gt;\u202f0.5, <jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>TP53<\/jats:italic> expression was significantly elevated in the PCAT of patients with CAD combined with T2DM, suggesting that this molecule plays a role in the development of this disease. Four first-order features and 10 texture features in the PCAT radiomic features were associated with abnormal <jats:italic>TP53<\/jats:italic> expression. The association of radiomic features with <jats:italic>TP53<\/jats:italic> suggests that CCTA-based radiomic features can be used to predict abnormalities in differential gene expression, thus providing a new way to noninvasively predict CAD combined with T2DM.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1626390","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T05:29:33Z","timestamp":1758518973000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["TP53 expression in PCAT in coronary artery disease combined with type 2 diabetes mellitus and its correlation with CCTA radiomic features: novel imaging biomarkers"],"prefix":"10.3389","volume":"12","author":[{"given":"Haicheng","family":"Qi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yahui","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiumei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Xing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"key":"ref1","volume-title":"Global Health estimates 2023: Deaths by cause, age, sex, by country and by region, 2000\u20132023","year":"2023"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e153","DOI":"10.1161\/CIR.0000000000001052","article-title":"Heart disease and stroke statistics-2022 update: a report from the American Heart Association","volume":"145","author":"Tsao","year":"2022","journal-title":"Circulation"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","article-title":"Global burden of cardiovascular diseases and risk factors, 1990-2019: update from the GBD 2019 study","volume":"76","author":"Roth","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/S0140-6736(23)01301-6","article-title":"Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the global burden of disease study 2021","volume":"402","year":"2023","journal-title":"Lancet"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"188556","DOI":"10.1016\/j.bbcan.2021.188556","article-title":"Tumor suppressor p53: biology, signaling pathways, and therapeutic targeting","volume":"1876","author":"Hern\u00e1ndez Borrero","year":"2021","journal-title":"Biochim Biophys Acta Rev Cancer"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"2459","DOI":"10.1161\/CIRCULATIONAHA.116.022194","article-title":"Clinical update: cardiovascular disease in diabetes mellitus","volume":"133","author":"Low Wang","year":"2016","journal-title":"Circulation"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"765","DOI":"10.3390\/medicina60050765","article-title":"Coronary computed tomography angiography-derived modified Duke index is associated with Peri-coronary fat attenuation index and predicts severity of coronary inflammation","volume":"60","author":"Hala\u021biu","year":"2024","journal-title":"Medicina (Kaunas)"},{"key":"ref8","first-page":"1591","article-title":"CT or invasive coronary angiography in stable chest pain","volume-title":"N Engl J Med","author":"Maurovich-Horvat","year":"2022"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1148\/radiol.212644","article-title":"The relationship between enhancing left atrial adipose tissue at ct and recurrent atrial fibrillation","volume":"305","author":"Huber","year":"2022","journal-title":"Radiology"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"6028","DOI":"10.1007\/s00330-022-08781-9","article-title":"A preliminary coronary computed tomography angiography-based study of perivascular fat attenuation index: relation with epicardial adipose tissue and its distribution over the entire coronary vasculature","volume":"32","author":"Bao","year":"2022","journal-title":"Eur Radiol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"804","DOI":"10.3390\/ijms25020804","article-title":"Diabetic vasculopathy: molecular mechanisms and clinical insights","volume":"25","author":"Jia","year":"2024","journal-title":"Int J Mol Sci"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1186\/s12933-024-02199-x","article-title":"Coronary inflammation based on pericoronary adipose tissue attenuation in type 2 diabetic mellitus: effect of diabetes management","volume":"23","author":"Liu","year":"2024","journal-title":"Cardiovasc Diabetol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.acra.2024.08.022","article-title":"Predictive value of CCTA-based pericoronary adipose tissue imaging for major adverse cardiovascular events","volume":"32","author":"Wu","year":"2025","journal-title":"Acad 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Coll Cardiol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"5131","DOI":"10.2147\/JIR.S326716","article-title":"Platelet mediated inflammation in coronary artery disease with type 2 diabetes patients","volume":"4","author":"Johny","year":"2021","journal-title":"J Inflamm Res"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"2050312119871786","DOI":"10.1177\/2050312119871786","article-title":"Very low-density lipoprotein cholesterol is associated with extent and severity of coronary artery disease in patients with type 2 diabetes mellitus","volume":"7","author":"Jia","year":"2019","journal-title":"SAGE Open Med"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"20220885","DOI":"10.1259\/bjr.20220885","article-title":"Evaluation of pericoronary adipose tissue attenuation on CT","volume":"96","author":"Ma","year":"2023","journal-title":"Br J 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Immunol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e0169389","DOI":"10.1371\/journal.pone.0169389","article-title":"Lower frequency of HLA-DRB1 type 1 diabetes risk alleles in pediatric patients with MODY","volume":"12","author":"Urrutia","year":"2017","journal-title":"PLoS One"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"459","DOI":"10.2147\/DDDT.S395207","article-title":"Exploring the active compounds of traditional mongolian medicine baolier capsule (BLEC) in patients with coronary artery disease (CAD) based on network pharmacology analysis, molecular docking and experimental validation","volume":"17","author":"Wei","year":"2023","journal-title":"Drug Des Devel Ther"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.cytogfr.2022.04.002","article-title":"The roles of cell-cell and organ-organ crosstalk in the type 2 diabetes mellitus associated inflammatory 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