Circulating microRNAs

Potential Markers of Cardiotoxicity in Children and Young Adults Treated With Anthracycline Chemotherapy

Kasey J. Leger, David Leonard, Danelle Nielson, James A de Lemos, Pradeep P Mammen, Naomi J Winick

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

BACKGROUND: Biomarkers for early detection of anthracycline (AC)-induced cardiotoxicity may allow cardioprotective intervention before irreversible damage. Circulating microRNAs (miRNAs) are promising biomarkers of cardiovascular disease, however, have not been studied in the setting of AC-induced cardiotoxicity. This study aimed to identify AC-induced alterations in plasma miRNA expression in children and correlate expression with markers of cardiac injury.

METHODS AND RESULTS: Candidate plasma profiling of 24 miRNAs was performed in 33 children before and after a cycle of AC (n=24) or noncardiotoxic chemotherapy (n=9). Relative miRNA changes between the pre- and postcycle time points (6, 12, and 24 hours) were determined within each treatment group and compared across groups. Plasma miRNA expression patterns were further explored with respect to AC dose and high-sensitivity troponin T. Greater chemotherapy-induced dysregulation was observed in this panel of candidate, cardiac-related plasma miRNAs in patients receiving anthracyclines compared with those receiving noncardiotoxic chemotherapy (24-hour MANOVA; P=0.024). Specifically, plasma miRs-29b and -499 were upregulated 6 to 24 hours post-AC, and their postchemotherapy expression significantly correlated with AC dose. Patients with acute cardiomyocyte injury (high-sensitivity troponin T increase ≥5 ng/L from baseline) demonstrated higher expression of miR-29b and miR-499 post-AC compared with those without.

CONCLUSIONS: In this pilot study, cardiac-related plasma miRNAs are dysregulated following ACs. Plasma miR-29b and -499 are acutely elevated post-AC, with dose response relationships observed with anthracycline dose and markers of cardiac injury. Further evaluation of miRNAs may provide mechanistic insight into AC-induced cardiotoxicity and yield biomarkers to facilitate earlier intervention to mitigate cardiotoxicity.

Original languageEnglish (US)
JournalJournal of the American Heart Association
Volume6
Issue number4
DOIs
StatePublished - Apr 4 2017

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Anthracyclines
MicroRNAs
Young Adult
Drug Therapy
Troponin T
Biomarkers
Cardiotoxicity
Wounds and Injuries
Cardiac Myocytes
Cardiovascular Diseases

Keywords

  • anthracycline
  • cancer
  • cardiotoxicity
  • microRNA
  • pediatric

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

@article{0e1ff231b35d4c92bf375b120d920da5,
title = "Circulating microRNAs: Potential Markers of Cardiotoxicity in Children and Young Adults Treated With Anthracycline Chemotherapy",
abstract = "BACKGROUND: Biomarkers for early detection of anthracycline (AC)-induced cardiotoxicity may allow cardioprotective intervention before irreversible damage. Circulating microRNAs (miRNAs) are promising biomarkers of cardiovascular disease, however, have not been studied in the setting of AC-induced cardiotoxicity. This study aimed to identify AC-induced alterations in plasma miRNA expression in children and correlate expression with markers of cardiac injury.METHODS AND RESULTS: Candidate plasma profiling of 24 miRNAs was performed in 33 children before and after a cycle of AC (n=24) or noncardiotoxic chemotherapy (n=9). Relative miRNA changes between the pre- and postcycle time points (6, 12, and 24 hours) were determined within each treatment group and compared across groups. Plasma miRNA expression patterns were further explored with respect to AC dose and high-sensitivity troponin T. Greater chemotherapy-induced dysregulation was observed in this panel of candidate, cardiac-related plasma miRNAs in patients receiving anthracyclines compared with those receiving noncardiotoxic chemotherapy (24-hour MANOVA; P=0.024). Specifically, plasma miRs-29b and -499 were upregulated 6 to 24 hours post-AC, and their postchemotherapy expression significantly correlated with AC dose. Patients with acute cardiomyocyte injury (high-sensitivity troponin T increase ≥5 ng/L from baseline) demonstrated higher expression of miR-29b and miR-499 post-AC compared with those without.CONCLUSIONS: In this pilot study, cardiac-related plasma miRNAs are dysregulated following ACs. Plasma miR-29b and -499 are acutely elevated post-AC, with dose response relationships observed with anthracycline dose and markers of cardiac injury. Further evaluation of miRNAs may provide mechanistic insight into AC-induced cardiotoxicity and yield biomarkers to facilitate earlier intervention to mitigate cardiotoxicity.",
keywords = "anthracycline, cancer, cardiotoxicity, microRNA, pediatric",
author = "Leger, {Kasey J.} and David Leonard and Danelle Nielson and {de Lemos}, {James A} and Mammen, {Pradeep P} and Winick, {Naomi J}",
year = "2017",
month = "4",
day = "4",
doi = "10.1161/JAHA.116.004653",
language = "English (US)",
volume = "6",
journal = "Journal of the American Heart Association",
issn = "2047-9980",
publisher = "Wiley-Blackwell",
number = "4",

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T1 - Circulating microRNAs

T2 - Potential Markers of Cardiotoxicity in Children and Young Adults Treated With Anthracycline Chemotherapy

AU - Leger, Kasey J.

AU - Leonard, David

AU - Nielson, Danelle

AU - de Lemos, James A

AU - Mammen, Pradeep P

AU - Winick, Naomi J

PY - 2017/4/4

Y1 - 2017/4/4

N2 - BACKGROUND: Biomarkers for early detection of anthracycline (AC)-induced cardiotoxicity may allow cardioprotective intervention before irreversible damage. Circulating microRNAs (miRNAs) are promising biomarkers of cardiovascular disease, however, have not been studied in the setting of AC-induced cardiotoxicity. This study aimed to identify AC-induced alterations in plasma miRNA expression in children and correlate expression with markers of cardiac injury.METHODS AND RESULTS: Candidate plasma profiling of 24 miRNAs was performed in 33 children before and after a cycle of AC (n=24) or noncardiotoxic chemotherapy (n=9). Relative miRNA changes between the pre- and postcycle time points (6, 12, and 24 hours) were determined within each treatment group and compared across groups. Plasma miRNA expression patterns were further explored with respect to AC dose and high-sensitivity troponin T. Greater chemotherapy-induced dysregulation was observed in this panel of candidate, cardiac-related plasma miRNAs in patients receiving anthracyclines compared with those receiving noncardiotoxic chemotherapy (24-hour MANOVA; P=0.024). Specifically, plasma miRs-29b and -499 were upregulated 6 to 24 hours post-AC, and their postchemotherapy expression significantly correlated with AC dose. Patients with acute cardiomyocyte injury (high-sensitivity troponin T increase ≥5 ng/L from baseline) demonstrated higher expression of miR-29b and miR-499 post-AC compared with those without.CONCLUSIONS: In this pilot study, cardiac-related plasma miRNAs are dysregulated following ACs. Plasma miR-29b and -499 are acutely elevated post-AC, with dose response relationships observed with anthracycline dose and markers of cardiac injury. Further evaluation of miRNAs may provide mechanistic insight into AC-induced cardiotoxicity and yield biomarkers to facilitate earlier intervention to mitigate cardiotoxicity.

AB - BACKGROUND: Biomarkers for early detection of anthracycline (AC)-induced cardiotoxicity may allow cardioprotective intervention before irreversible damage. Circulating microRNAs (miRNAs) are promising biomarkers of cardiovascular disease, however, have not been studied in the setting of AC-induced cardiotoxicity. This study aimed to identify AC-induced alterations in plasma miRNA expression in children and correlate expression with markers of cardiac injury.METHODS AND RESULTS: Candidate plasma profiling of 24 miRNAs was performed in 33 children before and after a cycle of AC (n=24) or noncardiotoxic chemotherapy (n=9). Relative miRNA changes between the pre- and postcycle time points (6, 12, and 24 hours) were determined within each treatment group and compared across groups. Plasma miRNA expression patterns were further explored with respect to AC dose and high-sensitivity troponin T. Greater chemotherapy-induced dysregulation was observed in this panel of candidate, cardiac-related plasma miRNAs in patients receiving anthracyclines compared with those receiving noncardiotoxic chemotherapy (24-hour MANOVA; P=0.024). Specifically, plasma miRs-29b and -499 were upregulated 6 to 24 hours post-AC, and their postchemotherapy expression significantly correlated with AC dose. Patients with acute cardiomyocyte injury (high-sensitivity troponin T increase ≥5 ng/L from baseline) demonstrated higher expression of miR-29b and miR-499 post-AC compared with those without.CONCLUSIONS: In this pilot study, cardiac-related plasma miRNAs are dysregulated following ACs. Plasma miR-29b and -499 are acutely elevated post-AC, with dose response relationships observed with anthracycline dose and markers of cardiac injury. Further evaluation of miRNAs may provide mechanistic insight into AC-induced cardiotoxicity and yield biomarkers to facilitate earlier intervention to mitigate cardiotoxicity.

KW - anthracycline

KW - cancer

KW - cardiotoxicity

KW - microRNA

KW - pediatric

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U2 - 10.1161/JAHA.116.004653

DO - 10.1161/JAHA.116.004653

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VL - 6

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

SN - 2047-9980

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