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

被引:51
作者
Gu, Meng [1 ]
Zheng, Aibin [1 ]
Tu, Wenjuan [1 ]
Zhao, Jing [1 ]
Li, Lin [1 ]
Li, Mengmeng [2 ]
Han, Shuping [2 ]
Hu, Xiaoshan [2 ]
Zhu, Jingai [2 ]
Pan, Ya [2 ]
Xu, Jun [1 ]
Yu, Zhangbin [2 ]
机构
[1] Nantong Med Univ, Charigzhou Childrens Hosp, Dept Pediat, 468 Yanling East Rd, Changzhou 213003, Peoples R China
[2] Nanjing Med Univ, Nanjing Matern & Child Hlth Care Hosp, Dept Pediat, 123 Tian Fei Xiang,Mo Chou Rd, Nanjing 210004, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Maternal plasma; Long non-coding RNA; Congenital heart defects; Gene ontology analysis; Signal pathway; Biomarker; LONG NONCODING RNAS; DILATED CARDIOMYOPATHY; DISEASE; EXPRESSION; CARCINOMA; GENOME;
D O I
10.1159/000443088
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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
引用
收藏
页码:1459 / 1471
页数:13
相关论文
共 25 条
[1]   Transcriptome Complexity in Cardiac Development and Diseases - An Expanding Universe Between Genome and Phenome [J].
Gao, Chen ;
Wang, Yibin .
CIRCULATION JOURNAL, 2014, 78 (05) :1038-1047
[2]   Long Non-Coding RNA Deregulation in Tongue Squamous Cell Carcinoma [J].
Gao, Wei ;
Chan, Jimmy Yu-Wai ;
Wong, Thian-Sze .
BIOMED RESEARCH INTERNATIONAL, 2014, 2014
[3]   miRNA in Plasma Exosome is Stable under Different Storage Conditions [J].
Ge, Qinyu ;
Zhou, Youxia ;
Lu, Jiafeng ;
Bai, Yunfei ;
Xie, Xueying ;
Lu, Zuhong .
MOLECULES, 2014, 19 (02) :1568-1575
[4]  
Gelb BD, 2011, CLIN INVESTIGATOR, V121, P844
[5]   Folbp1 promotes embryonic myocardial cell proliferation and apoptosis through the WNT signal transduction pathway [J].
Han, Shu-Ping ;
Pan, Ya ;
Peng, Yu-Zhu ;
Gu, Xiao-Qi ;
Chen, Rong-Hua ;
Guo, Xi-Rong .
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2009, 23 (03) :321-330
[6]   Long non-coding RNAs and human disease [J].
Harries, Lorna W. .
BIOCHEMICAL SOCIETY TRANSACTIONS, 2012, 40 :902-906
[7]  
Kushner DS, 1958, AM MED ASS, V166, P2162
[8]   Transcriptome Analysis Reveals Distinct Patterns of Long Noncoding RNAs in Heart and Plasma of Mice with Heart Failure [J].
Li, Danhua ;
Chen, Geng ;
Yang, Jichun ;
Fan, Xiaofang ;
Gong, Yongsheng ;
Xu, Guoheng ;
Cui, Qinghua ;
Geng, Bin .
PLOS ONE, 2013, 8 (10)
[9]   Plasma Levels of Acylated Ghrelin in Children with Pulmonary Hypertension Associated with Congenital Heart Disease [J].
Li, Gang ;
Xia, Jiyi ;
Jia, Peng ;
Zhao, Jian ;
Sun, Yuqin ;
Wu, Changxue ;
Liu, Bin .
PEDIATRIC CARDIOLOGY, 2015, 36 (07) :1423-1428
[10]   HULC and Linc00152 Act as Novel Biomarkers in Predicting Diagnosis of Hepatocellular Carcinoma [J].
Li, Jun ;
Wang, Xiaochen ;
Tang, Junwei ;
Jiang, Runqiu ;
Zhang, Wenjie ;
Ji, Jie ;
Sun, Beicheng .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2015, 37 (02) :687-696