{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T17:57:32Z","timestamp":1762451852271,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Resident Foundation at Aalborg University Hospital"},{"name":"Speciall\u00e6ge Heinrick Koops Foundation, Aase"},{"name":"Ejnar Danielsens Foundation"},{"name":"Blegdalens Foundation"},{"name":"Marie Pedersen and Jensine Heibergs Foundation"},{"name":"Medical Advancement of Science Foundation"},{"name":"Beckett Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cell-free DNA (cfDNA) promoter hypermethylation shows promise as a blood-based biomarker for pancreatic cancer, and similar alterations may occur in acute pancreatitis (AP). This study investigated the cfDNA hypermethylation profile of AP patients over time, compared with healthy controls, and its association with AP severity markers. A prospective longitudinal study including hospitalized AP patients and healthy controls was conducted. Methylation-specific PCR of a 23-gene panel was performed on plasma collected at inclusion (T0), 6 weeks (T6W), 6 months (T6M), and 7\u20138 years (T8Y). Associations between gene hypermethylation and clinical markers of AP severity\u2014CRP, leukocyte count, creatinine, hospital stay, and complications\u2014were evaluated. AP patients had a significantly higher mean number of hypermethylated genes at T0 (7.4, 95% CI: 6.8\u20138.0) compared with the controls (3.3, 95% CI: 2.8\u20133.8; p &lt; 0.01). The mean number decreased over time to 3.2 (95% CI: 2.4\u20134.1) at T8Y. Total hypermethylation was positively associated with CRP (\u03c1 = 0.39; p = 0.0018), leukocytes (\u03c1 = 0.35; p = 0.0052), and hospital stay (\u03c1 = 0.27; p = 0.0375). AP patients exhibited significantly higher cfDNA hypermethylation at disease onset, which normalized over time. Total hypermethylation showed positive associations with several markers of AP severity.<\/jats:p>","DOI":"10.3390\/ijms262110792","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T17:51:43Z","timestamp":1762451503000},"page":"10792","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cell-Free DNA Hypermethylation in Patients with Acute Pancreatitis"],"prefix":"10.3390","volume":"26","author":[{"given":"Hassan","family":"Al-Mashat","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery, Aalborg University Hospital, 9000 Aalborg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9557-1022","authenticated-orcid":false,"given":"Daniel Roger","family":"Baddoo","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Aalborg University Hospital, 9000 Aalborg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9420-2783","authenticated-orcid":false,"given":"S\u00f8ren","family":"Lundbye-Christensen","sequence":"additional","affiliation":[{"name":"Research Data and Biostatistics, Aalborg University Hospital, 9000 Aalborg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Poul Henning","family":"Madsen","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnostics, Aalborg University Hospital, 9000 Aalborg, Denmark"},{"name":"Department of Clinical Medicine, Aalborg University, 9000 Aalborg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9902-8040","authenticated-orcid":false,"given":"Inge S\u00f8kilde","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnostics, Aalborg University Hospital, 9000 Aalborg, Denmark"},{"name":"Department of Clinical Medicine, Aalborg University, 9000 Aalborg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5294-2428","authenticated-orcid":false,"given":"Henrik B.","family":"Krarup","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnostics, Aalborg University Hospital, 9000 Aalborg, Denmark"},{"name":"Department of Clinical Medicine, Aalborg University, 9000 Aalborg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2727-5915","authenticated-orcid":false,"given":"Benjamin Emil","family":"Stubbe","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Aalborg University Hospital, 9000 Aalborg, Denmark"},{"name":"Department of Clinical Medicine, Aalborg University, 9000 Aalborg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ole","family":"Thorlacius-Ussing","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Aalborg University Hospital, 9000 Aalborg, Denmark"},{"name":"Department of Clinical Medicine, Aalborg University, 9000 Aalborg, Denmark"},{"name":"Clinical Cancer Research Center, Aalborg University Hospital, 9000 Aalborg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0286-397X","authenticated-orcid":false,"given":"Stine Dam","family":"Henriksen","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Aalborg University Hospital, 9000 Aalborg, Denmark"},{"name":"Department of Clinical Medicine, Aalborg University, 9000 Aalborg, Denmark"},{"name":"Clinical Cancer Research Center, Aalborg University Hospital, 9000 Aalborg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S2468-1253(16)30004-8","article-title":"Global incidence and mortality of pancreatic diseases: A systematic review, meta-analysis, and meta-regression of population-based cohort studies","volume":"1","author":"Xiao","year":"2016","journal-title":"Lancet Gastroenterol. 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