Circulating LncRNAs as Novel, Non-Invasive Biomarkers for Prenatal Detection of Fetal Congenital Heart Defects

Objectives: To explore the clinical value of circulating long non-coding RNAs (IncRNAs) as biomarkers to predict fetal congenital heart defects (CHD) in pregnant women. Methods: Differential expression of IncRNAs isolated from the plasma of pregnant women with typical fetal CHD or healthy controls was analyzed by microarray. Gene ontology (GO), pathway and network analysis were performed to study the function of the IncRNAs. Differentially expressed IncRNAs were validated in plasma samples from 62 pregnant women with typical CHD and 62 matched controls by RT-PCR. The sensitivity and specificity of each IncRNA in the diagnosis of fetal CHD was determined by ROC curve analysis. Results: Microarray analysis identified 3694 up-regulated and 3919 down-regulated (fold change >= 2.0) IncRNAs. The top ten significantly differentially expressed, CHD-associated IncRNAs were validated by RT-PCR. Five significantly up-regulated or down-regulated IncRNAs were identified: ENST00000436681, EN5T00000422826, AA584040, AA709223 and BX478947 with the AUC of ROC curves calculated as 0.892, 0.817, 0.755, 0.882 and 0.886, respectively. Conclusions: Specific IncRNAs aberrantly expressed in the plasma of pregnant women with typical fetal CHD may play a key role in the development of CHD and may be used as novel biomarkers for prenatal diagnosis of fetal CHD. (C) 2016 The Author(s) Published by S. Karger AG, Basel