Candidate Plasma Biomarkers to Detect Anthracycline‐Related Cardiomyopathy in Childhood Cancer Survivors: A Case Control Study in the Dutch Childhood Cancer Survivor Study

Media type: E-Article
Title: Candidate Plasma Biomarkers to Detect Anthracycline‐Related Cardiomyopathy in Childhood Cancer Survivors: A Case Control Study in the Dutch Childhood Cancer Survivor Study
Contributor: Leerink, Jan M.; Feijen, Elizabeth A. M.; Moerland, Perry D.; de Baat, Esmee C.; Merkx, Remy; van der Pal, Helena J. H.; Tissing, Wim J. E.; Louwerens, Marloes; van den Heuvel‐Eibrink, Marry M.; Versluys, A. Birgitta; Asselbergs, Folkert W.; Sammani, Arjan; Teske, Arco J.; van Dalen, Elvira C.; van der Heiden‐van der Loo, Margriet; van Dulmen‐den Broeder, Eline; de Vries, Andrica C. H.; Kapusta, Livia; Loonen, Jacqueline; Pinto, Yigal M.; Kremer, Leontien C. M.; Mavinkurve‐Groothuis, Annelies M. C.; Kok, Wouter E. M.
imprint: Ovid Technologies (Wolters Kluwer Health), 2022
Published in: Journal of the American Heart Association
Language: English
DOI: 10.1161/jaha.121.025935
ISSN: 2047-9980
Keywords: Cardiology and Cardiovascular Medicine
Origination:
Footnote:
Description: <jats:sec sec-type="background" xml:lang="en"> <jats:title>Background</jats:title> <jats:p xml:lang="en">Plasma biomarkers may aid in the detection of anthracycline‐related cardiomyopathy (ACMP). However, the currently available biomarkers have limited diagnostic value in long‐term childhood cancer survivors. This study sought to identify diagnostic plasma biomarkers for ACMP in childhood cancer survivors.</jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Methods and Results</jats:title> <jats:p xml:lang="en"> We measured 275 plasma proteins in 28 ACMP cases with left ventricular ejection fraction <45%, 29 anthracycline‐treated controls with left ventricular ejection fraction ≥53% matched on sex, time after cancer, and anthracycline dose, and 29 patients with genetically determined dilated cardiomyopathy with left ventricular ejection fraction <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‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) and the inflammatory markers CCL19 (C‐C motif chemokine ligands 19) and CCL20, PSPD (pulmonary surfactant protein‐D), and PTN (pleiotrophin) were significantly upregulated in ACMP compared with controls. An elastic net model selected 45 proteins, including NT‐proBNP, 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‐proBNP and clinical characteristics (AUC=0.75; <jats:italic>P</jats:italic> =0.766). However, when excluding 8 ACMP cases with heart failure, the full model was superior to that including only NT‐proBNP and clinical characteristics (AUC=0.75 versus AUC=0.50; <jats:italic>P</jats:italic> =0.022). The same 45 proteins also showed good discrimination between dilated cardiomyopathy and controls (AUC=0.89), underscoring their association with cardiomyopathy. </jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Conclusions</jats:title> <jats:p xml:lang="en">We identified 3 specific inflammatory proteins as candidate plasma biomarkers for ACMP in long‐term childhood cancer survivors and demonstrated protein overlap with dilated cardiomyopathy.</jats:p> </jats:sec>
Access State: Open Access

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