Candidate Plasma Biomarkers to Detect Anthracycline-Related Cardiomyopathy in Childhood Cancer Survivors: A Case Control Study in the Dutch Childhood Cancer Survivor Study
BACKGROUND: Plasma biomarkers may aid in the detection of anthracycline-related cardiomyopathy (ACMP). However, the cur-rently 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. METHODS AND RESULTS: 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 anthracy-cline dose, and 29 patients with gen... Mehr ...
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Dokumenttyp: | Artikel |
Erscheinungsdatum: | 2022 |
Verlag/Hrsg.: |
WILEY
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Schlagwörter: | anthracycline-related cardiomyopathy / biomarkers / cancer therapy-related cardiac dysfunction / cardio-oncology / chemokine ligands / childhood cancer survivors |
Sprache: | Englisch |
Permalink: | https://search.fid-benelux.de/Record/base-26663582 |
Datenquelle: | BASE; Originalkatalog |
Powered By: | BASE |
Link(s) : | https://discovery.ucl.ac.uk/id/eprint/10158625/1/JAHA.121.025935.pdf |
BACKGROUND: Plasma biomarkers may aid in the detection of anthracycline-related cardiomyopathy (ACMP). However, the cur-rently 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. METHODS AND RESULTS: 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 anthracy-cline 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 char-acteristics, 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; P=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; P=0.022). The same 45 proteins also showed good discrimination between dilated cardiomyopathy and controls (AUC=0.89), underscoring their association with cardiomyopathy. CONCLUSIONS: 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.