Clinical significance of circulating microRNAs as markers in detecting and predicting congenital heart defects in children

Yong Song, Hilda Higgins, Jing Guo, Katrina Harrison, E. N. Schultz, Belinda J. Hales, Eric K. Moses, Jack Goldblatt, Nicholas Pachter, Guicheng Zhang

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Circulating microRNAs (miRNAs) are emerging as novel biomarkers for detecting cardiovascular diseases. In this study, we aimed to investigate the usefulness of miRNAs as biomarkers in diagnosing and predicting children with congenital heart defects (CHD), particularly in the context of multiple subtypes of CHD. Methods: We recruited 26 families, each having a child with CHD and parents who do not have any cardiovascular disorder. 27 families unaffected by cardiovascular disease were also included as controls. Firstly, we screened 84 circulating miRNAs relating to cardiovascular development in 6 children with atrial septal defects (ASD) and 5 healthy children. We validated the selected miRNAs with differential expression in a larger sample size (n = 27 for controls, n = 26 for cases), and evaluated their signal in different types of septal defects. Finally, we examined the identified miRNAs signatures in the parent population and assessed their diagnostic values for predicting CHD. Results: The three miRNAs hsa-let-7a, hsa-let-7b and hsa-miR-486 were significantly upregulated in children with ASD. A further validation study showed that overexpression of hsa-let-7a and hsa-let-7b was specifically present in ASD children, but not in children with other subtypes of septal defects. A similar expression profile of hsa-let-7a and hsa-let-7b was discovered in mothers of ASD children. Receiver-operating characteristic curve analyses indicated that hsa-let-7a and hsa-let-7b had significant diagnostic values for detecting ASD and in maternal samples predicting the occurrence of ASD in offspring. Conclusions: Circulating miRNAs are important markers not only for diagnosing CHD, but also for predicting CHD risk in offspring. The distinct miRNA signatures are likely to present in various subtypes of CHD, and the phenotypic heterogeneity of CHD should be considered to develop such miRNA-based assays. © 2018 The Author(s).
Original languageEnglish
Article number42
JournalJournal of Translational Medicine
Volume16
Issue number1
DOIs
Publication statusPublished - 27 Feb 2018

Fingerprint

Congenital Heart Defects
MicroRNAs
Atrial Heart Septal Defects
Defects
Cardiovascular Diseases
Biomarkers
Mothers
Validation Studies
ROC Curve
Sample Size
Parents

Cite this

@article{f69eb1aab0c74b45aca0b3984d02d569,
title = "Clinical significance of circulating microRNAs as markers in detecting and predicting congenital heart defects in children",
abstract = "Background: Circulating microRNAs (miRNAs) are emerging as novel biomarkers for detecting cardiovascular diseases. In this study, we aimed to investigate the usefulness of miRNAs as biomarkers in diagnosing and predicting children with congenital heart defects (CHD), particularly in the context of multiple subtypes of CHD. Methods: We recruited 26 families, each having a child with CHD and parents who do not have any cardiovascular disorder. 27 families unaffected by cardiovascular disease were also included as controls. Firstly, we screened 84 circulating miRNAs relating to cardiovascular development in 6 children with atrial septal defects (ASD) and 5 healthy children. We validated the selected miRNAs with differential expression in a larger sample size (n = 27 for controls, n = 26 for cases), and evaluated their signal in different types of septal defects. Finally, we examined the identified miRNAs signatures in the parent population and assessed their diagnostic values for predicting CHD. Results: The three miRNAs hsa-let-7a, hsa-let-7b and hsa-miR-486 were significantly upregulated in children with ASD. A further validation study showed that overexpression of hsa-let-7a and hsa-let-7b was specifically present in ASD children, but not in children with other subtypes of septal defects. A similar expression profile of hsa-let-7a and hsa-let-7b was discovered in mothers of ASD children. Receiver-operating characteristic curve analyses indicated that hsa-let-7a and hsa-let-7b had significant diagnostic values for detecting ASD and in maternal samples predicting the occurrence of ASD in offspring. Conclusions: Circulating miRNAs are important markers not only for diagnosing CHD, but also for predicting CHD risk in offspring. The distinct miRNA signatures are likely to present in various subtypes of CHD, and the phenotypic heterogeneity of CHD should be considered to develop such miRNA-based assays. {\circledC} 2018 The Author(s).",
author = "Yong Song and Hilda Higgins and Jing Guo and Katrina Harrison and Schultz, {E. N.} and Hales, {Belinda J.} and Moses, {Eric K.} and Jack Goldblatt and Nicholas Pachter and Guicheng Zhang",
year = "2018",
month = "2",
day = "27",
doi = "10.1186/s12967-018-1411-0",
language = "English",
volume = "16",
journal = "Journal of Translational Medicine",
issn = "1479-5876",
publisher = "BioMed Central",
number = "1",

}

Clinical significance of circulating microRNAs as markers in detecting and predicting congenital heart defects in children. / Song, Yong; Higgins, Hilda; Guo, Jing; Harrison, Katrina; Schultz, E. N.; Hales, Belinda J.; Moses, Eric K.; Goldblatt, Jack; Pachter, Nicholas; Zhang, Guicheng.

In: Journal of Translational Medicine, Vol. 16, No. 1, 42, 27.02.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Clinical significance of circulating microRNAs as markers in detecting and predicting congenital heart defects in children

AU - Song, Yong

AU - Higgins, Hilda

AU - Guo, Jing

AU - Harrison, Katrina

AU - Schultz, E. N.

AU - Hales, Belinda J.

AU - Moses, Eric K.

AU - Goldblatt, Jack

AU - Pachter, Nicholas

AU - Zhang, Guicheng

PY - 2018/2/27

Y1 - 2018/2/27

N2 - Background: Circulating microRNAs (miRNAs) are emerging as novel biomarkers for detecting cardiovascular diseases. In this study, we aimed to investigate the usefulness of miRNAs as biomarkers in diagnosing and predicting children with congenital heart defects (CHD), particularly in the context of multiple subtypes of CHD. Methods: We recruited 26 families, each having a child with CHD and parents who do not have any cardiovascular disorder. 27 families unaffected by cardiovascular disease were also included as controls. Firstly, we screened 84 circulating miRNAs relating to cardiovascular development in 6 children with atrial septal defects (ASD) and 5 healthy children. We validated the selected miRNAs with differential expression in a larger sample size (n = 27 for controls, n = 26 for cases), and evaluated their signal in different types of septal defects. Finally, we examined the identified miRNAs signatures in the parent population and assessed their diagnostic values for predicting CHD. Results: The three miRNAs hsa-let-7a, hsa-let-7b and hsa-miR-486 were significantly upregulated in children with ASD. A further validation study showed that overexpression of hsa-let-7a and hsa-let-7b was specifically present in ASD children, but not in children with other subtypes of septal defects. A similar expression profile of hsa-let-7a and hsa-let-7b was discovered in mothers of ASD children. Receiver-operating characteristic curve analyses indicated that hsa-let-7a and hsa-let-7b had significant diagnostic values for detecting ASD and in maternal samples predicting the occurrence of ASD in offspring. Conclusions: Circulating miRNAs are important markers not only for diagnosing CHD, but also for predicting CHD risk in offspring. The distinct miRNA signatures are likely to present in various subtypes of CHD, and the phenotypic heterogeneity of CHD should be considered to develop such miRNA-based assays. © 2018 The Author(s).

AB - Background: Circulating microRNAs (miRNAs) are emerging as novel biomarkers for detecting cardiovascular diseases. In this study, we aimed to investigate the usefulness of miRNAs as biomarkers in diagnosing and predicting children with congenital heart defects (CHD), particularly in the context of multiple subtypes of CHD. Methods: We recruited 26 families, each having a child with CHD and parents who do not have any cardiovascular disorder. 27 families unaffected by cardiovascular disease were also included as controls. Firstly, we screened 84 circulating miRNAs relating to cardiovascular development in 6 children with atrial septal defects (ASD) and 5 healthy children. We validated the selected miRNAs with differential expression in a larger sample size (n = 27 for controls, n = 26 for cases), and evaluated their signal in different types of septal defects. Finally, we examined the identified miRNAs signatures in the parent population and assessed their diagnostic values for predicting CHD. Results: The three miRNAs hsa-let-7a, hsa-let-7b and hsa-miR-486 were significantly upregulated in children with ASD. A further validation study showed that overexpression of hsa-let-7a and hsa-let-7b was specifically present in ASD children, but not in children with other subtypes of septal defects. A similar expression profile of hsa-let-7a and hsa-let-7b was discovered in mothers of ASD children. Receiver-operating characteristic curve analyses indicated that hsa-let-7a and hsa-let-7b had significant diagnostic values for detecting ASD and in maternal samples predicting the occurrence of ASD in offspring. Conclusions: Circulating miRNAs are important markers not only for diagnosing CHD, but also for predicting CHD risk in offspring. The distinct miRNA signatures are likely to present in various subtypes of CHD, and the phenotypic heterogeneity of CHD should be considered to develop such miRNA-based assays. © 2018 The Author(s).

U2 - 10.1186/s12967-018-1411-0

DO - 10.1186/s12967-018-1411-0

M3 - Article

VL - 16

JO - Journal of Translational Medicine

JF - Journal of Translational Medicine

SN - 1479-5876

IS - 1

M1 - 42

ER -