{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T17:07:11Z","timestamp":1789837631732,"version":"4.0.1"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2021,12,5]],"date-time":"2021-12-05T00:00:00Z","timestamp":1638662400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Primary sclerosing cholangitis (PSC) is associated with increased risk of cholangiocarcinoma (CCA). Early and accurate CCA detection represents an unmet clinical need as the majority of patients with PSC are diagnosed at an advanced stage of malignancy. In the present study, we aimed at establishing robust DNA methylation biomarkers in bile for early and accurate diagnosis of CCA in PSC.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>Droplet digital PCR (ddPCR) was used to analyze\u00a0344 bile samples from 273 patients with sporadic and PSC\u2010associated CCA, PSC, and other nonmalignant liver diseases for promoter methylation of cysteine dioxygenase type 1, cannabinoid receptor interacting protein 1, septin 9, and vimentin. Receiver operating characteristic (ROC) curve analyses revealed high AUCs for all four markers (0.77\u20130.87) for CCA detection among patients with PSC. Including only samples from patients with PSC diagnosed with CCA \u2264 12\u00a0months following bile collection increased the accuracy for cancer detection, with a combined sensitivity of 100% (28\/28) and a specificity of 90% (20\/203). The specificity increased to 93% when only including patients with PSC with longtime follow\u2010up (&gt; 36\u00a0months) as controls, and remained high (83%) when only including patients with PSC and dysplasia as controls (<jats:italic toggle=\"yes\">n<\/jats:italic>\u00a0=\u00a023). Importantly, the bile samples from the CCA\u2010PSC \u2264 12 patients, all positive for the biomarkers, included both early\u2010stage and late\u2010stage CCA, different tumor growth patterns, anatomical locations, and carbohydrate antigen 19\u20109 levels.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Using highly sensitive ddPCR to analyze robust epigenetic biomarkers, CCA in PSC was accurately detected in bile, irrespective of clinical and molecular features, up to 12\u00a0months before CCA diagnosis. The findings suggest a potential for these biomarkers to complement current detection and screening methods for CCA in patients with PSC.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.32125","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T05:41:37Z","timestamp":1629956497000},"page":"59-73","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":49,"title":["Early and accurate detection of cholangiocarcinoma in patients with primary sclerosing cholangitis by methylation markers in bile"],"prefix":"10.1097","volume":"75","author":[{"given":"Hege Marie","family":"Vedeld","sequence":"first","affiliation":[{"name":"Department of Molecular Oncology,Institute for Cancer Research,Oslo University Hospital\u2013Norwegian Radium Hospital,Oslo,Norway"},{"name":"K.\u00a0G. Jebsen Colorectal Cancer Research Centre,Oslo University Hospital,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marit M.","family":"Grimsrud","sequence":"additional","affiliation":[{"name":"Norwegian PSC Research Center, Department of Transplantation Medicine,Oslo University Hospital,Oslo,Norway"},{"name":"Institute of Clinical Medicine,University of Oslo,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Andresen","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology,Institute for Cancer Research,Oslo University Hospital\u2013Norwegian Radium Hospital,Oslo,Norway"},{"name":"K.\u00a0G. Jebsen Colorectal Cancer Research Centre,Oslo University Hospital,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi D.","family":"Pharo","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology,Institute for Cancer Research,Oslo University Hospital\u2013Norwegian Radium Hospital,Oslo,Norway"},{"name":"K.\u00a0G. Jebsen Colorectal Cancer Research Centre,Oslo University Hospital,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"von Seth","sequence":"additional","affiliation":[{"name":"Department of Medicine Huddinge,Unit of Gastroenterology and Rheumatology,Karolinska Institutet,Karolinska University Hospital,Stockholm,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom H.","family":"Karlsen","sequence":"additional","affiliation":[{"name":"Norwegian PSC Research Center, Department of Transplantation Medicine,Oslo University Hospital,Oslo,Norway"},{"name":"Institute of Clinical Medicine,University of Oslo,Oslo,Norway"},{"name":"Section of Gastroenterology,Department of Transplantation Medicine,Division of Surgery, Inflammatory Medicine and Transplantation,Oslo University Hospital\u2013Rikshospitalet,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilde","family":"Honne","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology,Institute for Cancer Research,Oslo University Hospital\u2013Norwegian Radium Hospital,Oslo,Norway"},{"name":"K.\u00a0G. Jebsen Colorectal Cancer Research Centre,Oslo University Hospital,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vemund","family":"Paulsen","sequence":"additional","affiliation":[{"name":"Section of Gastroenterology,Department of Transplantation Medicine,Division of Surgery, Inflammatory Medicine and Transplantation,Oslo University Hospital\u2013Rikshospitalet,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martti A.","family":"F\u00e4rkkil\u00e4","sequence":"additional","affiliation":[{"name":"Department of Medicine,Division of Gastroenterology,Helsinki University Hospital and Helsinki University,Helsinki,Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Bergquist","sequence":"additional","affiliation":[{"name":"Department of Medicine Huddinge,Unit of Gastroenterology and Rheumatology,Karolinska Institutet,Karolinska University Hospital,Stockholm,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marine","family":"Jeanmougin","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology,Institute for Cancer Research,Oslo University Hospital\u2013Norwegian Radium Hospital,Oslo,Norway"},{"name":"K.\u00a0G. Jebsen Colorectal Cancer Research Centre,Oslo University Hospital,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Aabakken","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine,University of Oslo,Oslo,Norway"},{"name":"Section of Gastroenterology,Department of Transplantation Medicine,Division of Surgery, Inflammatory Medicine and Transplantation,Oslo University Hospital\u2013Rikshospitalet,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten M.","family":"Boberg","sequence":"additional","affiliation":[{"name":"Norwegian PSC Research Center, Department of Transplantation Medicine,Oslo University Hospital,Oslo,Norway"},{"name":"Institute of Clinical Medicine,University of Oslo,Oslo,Norway"},{"name":"Section of Gastroenterology,Department of Transplantation Medicine,Division of Surgery, Inflammatory Medicine and Transplantation,Oslo University Hospital\u2013Rikshospitalet,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trine","family":"Folseraas","sequence":"additional","affiliation":[{"name":"Norwegian PSC Research Center, Department of Transplantation Medicine,Oslo University Hospital,Oslo,Norway"},{"name":"Section of Gastroenterology,Department of Transplantation Medicine,Division of Surgery, Inflammatory Medicine and Transplantation,Oslo University Hospital\u2013Rikshospitalet,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guro E.","family":"Lind","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology,Institute for Cancer Research,Oslo University Hospital\u2013Norwegian Radium Hospital,Oslo,Norway"},{"name":"K.\u00a0G. 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