{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T02:00:12Z","timestamp":1791770412426,"version":"4.3.4"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"14","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,7,19]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Plasma biomarkers may aid in the detection of anthracycline\u2010related cardiomyopathy (ACMP). However, the currently available biomarkers have limited diagnostic value in long\u2010term childhood cancer survivors. This study sought to identify diagnostic plasma biomarkers for ACMP in childhood cancer survivors.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We measured 275 plasma proteins in 28 ACMP cases with left ventricular ejection fraction &lt;45%, 29 anthracycline\u2010treated controls with left ventricular ejection fraction \u226553% matched on sex, time after cancer, and anthracycline dose, and 29 patients with genetically determined dilated cardiomyopathy with left ventricular ejection fraction &lt;45%. Multivariable linear regression was used to identify differentially expressed proteins. Elastic net model, including clinical characteristics, was used to assess discrimination of proteins diagnostic for ACMP. NT\u2010proBNP (N\u2010terminal pro\u2010B\u2010type natriuretic peptide) and the inflammatory markers CCL19 (C\u2010C motif chemokine ligands 19) and CCL20, PSPD (pulmonary surfactant protein\u2010D), and PTN (pleiotrophin) were significantly upregulated in ACMP compared with controls. An elastic net model selected 45 proteins, including NT\u2010proBNP, CCL19, CCL20 and PSPD, but not PTN, that discriminated ACMP cases from controls with an area under the receiver operating characteristic curve (AUC) of 0.78. This model was not superior to a model including NT\u2010proBNP and clinical characteristics (AUC=0.75;\n              <jats:italic>P<\/jats:italic>\n              =0.766). However, when excluding 8 ACMP cases with heart failure, the full model was superior to that including only NT\u2010proBNP and clinical characteristics (AUC=0.75 versus AUC=0.50;\n              <jats:italic>P<\/jats:italic>\n              =0.022). The same 45 proteins also showed good discrimination between dilated cardiomyopathy and controls (AUC=0.89), underscoring their association with cardiomyopathy.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">We identified 3 specific inflammatory proteins as candidate plasma biomarkers for ACMP in long\u2010term childhood cancer survivors and demonstrated protein overlap with dilated cardiomyopathy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.025935","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T09:58:48Z","timestamp":1657706328000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Candidate Plasma Biomarkers to Detect Anthracycline\u2010Related Cardiomyopathy in Childhood Cancer Survivors: A Case Control Study in the Dutch Childhood Cancer Survivor Study"],"prefix":"10.1161","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9413-8478","authenticated-orcid":false,"given":"Jan M.","family":"Leerink","sequence":"first","affiliation":[{"name":"Department of Cardiology, Amsterdam Cardiovascular Sciences Amsterdam University Medical Center, University of Amsterdam, Heart Center Amsterdam The Netherlands"},{"name":"Princess M\u00e1xima Center for Pediatric Oncology Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A. M.","family":"Feijen","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perry D.","family":"Moerland","sequence":"additional","affiliation":[{"name":"Bioinformatics Laboratory, Department of Epidemiology and Data Science Amsterdam University Medical Center, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esmee C.","family":"de Baat","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9853-7257","authenticated-orcid":false,"given":"Remy","family":"Merkx","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena J. H.","family":"van der Pal","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim J. E.","family":"Tissing","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology Utrecht The Netherlands"},{"name":"Beatrix Children\u2019s Hospital, Department of Pediatric Oncology University of Groningen, University Medical Center Groningen Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6748-3540","authenticated-orcid":false,"given":"Marloes","family":"Louwerens","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Leiden University Medical Center Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7760-879X","authenticated-orcid":false,"given":"Marry M.","family":"van den Heuvel\u2010Eibrink","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Birgitta","family":"Versluys","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1692-8669","authenticated-orcid":false,"given":"Folkert W.","family":"Asselbergs","sequence":"additional","affiliation":[{"name":"Division of Heart and Lungs, Department of Cardiology University Medical Center Utrecht Utrecht The Netherlands"},{"name":"Institute of Cardiovascular Science, Faculty of Population Health Sciences University College London London UK"},{"name":"Health Data Research UK and Institute of Health Informatics University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5557-9342","authenticated-orcid":false,"given":"Arjan","family":"Sammani","sequence":"additional","affiliation":[{"name":"Division of Heart and Lungs, Department of Cardiology University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arco J.","family":"Teske","sequence":"additional","affiliation":[{"name":"Division of Heart and Lungs, Department of Cardiology University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8886-6532","authenticated-orcid":false,"given":"Elvira C.","family":"van Dalen","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margriet","family":"van der Heiden\u2010van der Loo","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eline","family":"van Dulmen\u2010den Broeder","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology Amsterdam University Medical Center, Vrije Universiteit Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrica C. H.","family":"de Vries","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology Utrecht The Netherlands"},{"name":"Department of Pediatric Oncology Erasmus Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"Kapusta","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology Amalia Children\u2019s Hospital, Radboud University Medical Center Nijmegen The Netherlands"},{"name":"Sackler School of Medicine, Department of Pediatrics, Pediatric Cardiology Unit Tel Aviv Sourasky Medical Center, Tel Aviv University Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Loonen","sequence":"additional","affiliation":[{"name":"Department of Hematology Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yigal M.","family":"Pinto","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Amsterdam Cardiovascular Sciences Amsterdam University Medical Center, University of Amsterdam, Heart Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7422-3248","authenticated-orcid":false,"given":"Leontien C. 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