{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:19:19Z","timestamp":1785424759008,"version":"3.56.0"},"reference-count":29,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100022415","name":"Lillebaelt Hospital","doi-asserted-by":"crossref","award":["2024-0017"],"award-info":[{"award-number":["2024-0017"]}],"id":[{"id":"10.13039\/501100022415","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2024-0017"],"award-info":[{"award-number":["2024-0017"]}],"id":[{"id":"https:\/\/ror.org\/04jewc589","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100024075","name":"Region of Southern Denmark","doi-asserted-by":"crossref","award":["2024-0118"],"award-info":[{"award-number":["2024-0118"]}],"id":[{"id":"10.13039\/501100024075","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2024-0118"],"award-info":[{"award-number":["2024-0118"]}],"id":[{"id":"https:\/\/ror.org\/0290a6k23","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Prostate cancer (PCa) exhibits marked biological heterogeneity, complicating accurate identification of aggressive disease at initial diagnosis. This study investigated whether circulating tumour DNA (ctDNA) methylation markers enhance detection and risk stratification across the PCa disease continuum. Plasma samples from the initial hospital visit were obtained from 280 participants in the PerPros prostate biobank (Vejle, Denmark), all referred with suspected PCa. Following diagnostic work-up, participants were classified across the PCa disease spectrum or as biopsy-confirmed PCa-free controls. Five methylated CpG regions (DOCK2, HAPLN3, ACTRT2, EVX1, HOXD13) were analysed using multiplex ddPCR. Performance was assessed using ROC analysis and logistic regression and compared with prostate-specific antigen (PSA). Methylation markers were detectable across the PCa disease spectrum, most frequently in metastatic castration-sensitive PCa (mCSPC) (85\/97; 88%). The ctDNA methylation panel discriminated mCSPC from controls with an AUC (area under the curve) of 0.88 (95% CI: 0.83\u20130.93). In this cohort, combining PSA (cut-off 20 \u00b5g\/L) with the ctDNA methylation panel significantly improved discrimination between patients with mCSPC and locally advanced PCa compared with PSA alone (AUC 0.88; 95% CI 0.83\u20130.94; p &lt; 0.001) vs. 0.78 (95% CI 0.71\u20130.84). In contrast, discrimination between localised\/locally advanced PCa and patients with biopsy-confirmed controls was limited (AUC 0.56; 95% CI: 0.51\u20130.61). The ctDNA methylation panel demonstrates robust identification of metastatic PCa and can effectively differentiate mCSPC from locally advanced PCa. However, its diagnostic abilities in localised disease appear limited.<\/jats:p>","DOI":"10.3390\/ijms27136081","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T09:53:46Z","timestamp":1783418026000},"page":"6081","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of a Methylated Circulating Tumour DNA Panel for Detection and Disease Stratification in Prostate Cancer"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2123-083X","authenticated-orcid":false,"given":"Stine V.","family":"Eriksen","sequence":"first","affiliation":[{"name":"Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark"},{"name":"Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, 5230 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8895-6394","authenticated-orcid":false,"given":"Ahmed H.","family":"Zedan","sequence":"additional","affiliation":[{"name":"Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9330-8734","authenticated-orcid":false,"given":"S\u00f8ren","family":"Kahns","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Vejle Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7962-1640","authenticated-orcid":false,"given":"Palle J. S.","family":"Osther","sequence":"additional","affiliation":[{"name":"Department of Urology, Vejle Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5862-7784","authenticated-orcid":false,"given":"Signe","family":"Timm","sequence":"additional","affiliation":[{"name":"Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7476-671X","authenticated-orcid":false,"given":"Torben F.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark"},{"name":"Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, 5230 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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