先天性心脏病, microRNA , 产前诊断, 血清标志物," /> 先天性心脏病, microRNA , 产前诊断, 血清标志物,"/> Congenital heart defect, microRNA, Prenatal diagnosis, Serum biomarker,"/> <span style="line-height:2;font-size:14px;">先天性心脏病胎儿母体血清中的microRNA</span><span style="line-height:2;font-size:14px;">表达谱及其诊断意义</span>
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发育医学电子杂志  2019, Vol. 7 Issue (1): 32-37    DOI: 10.3969/j.issn.2095-5340.2019.01.008
  围产医学   论著 |产科 |
先天性心脏病胎儿母体血清中的microRNA表达谱及其诊断意义
顾卉 陈骊珠 薛佳 黄天楚 袁正伟
1. 中国医科大学附属盛京医院 国家卫生健康委员会小儿先天畸形重点实验室,辽宁 沈阳 110004;2. 中国医科大学附属盛京医院 超声科,辽宁 沈阳 110004
microRNA expression profile in the serum of pregnant women with congenital heart disease fetuses and its diagnosis value
GU hui  CHEN Li-zhu  XUE Jia  HUANG Tian-chu  YUAN Zheng-wei
1.NHC Laboratory of Congenital Malformation, Shengjing Hospital of China Medical University, Liaoning, Shenyang 110004, China; 2.Department of Ultrasound, Shengjing Hospital of China Medical University, Liaoning, Shenyang 110004, China
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摘要 【摘要】 目的 筛选先天性心脏病胎儿的母体血清差异表达 microRNA(miRNA),确定先天性心脏病
的无创产前诊断候选标志物。 方法 2012 年 1 月至 2015 年 12 月,在中国医科大学附属盛京医院进
行产前超声检查并确诊为胎儿先天性心脏病的 50 例孕妇为研究对象;选取 50 例正常孕妇为对照组,孕周、孕妇年龄与先天性心脏病组相匹配。利用 miRNA 芯片对先天性心脏病胎儿的母体血清中差异表达的 miRNA 进行高通量筛选,并进一步用实时定量 PCR 方法在研究组与对照组胎儿母体血清中验证差异表达 miRNA。统计学分析采用独立样本 t 检验及受试者操作特性曲线。 结果 芯片方法在孕妇血清中共探测到 1 033 个人类 miRNA,研究组与对照组中差异倍数高于 2 倍以上的 miRNA 共 38 个。生物信息学信号通路分析显示最相关的为心肌细胞中的肾上腺素信号通路和 AMPK 信号通路。4 个miRNA(miR-3199、miR-125b-2-3p、miR-4666a-3p 和 miR-4681)在先天性心脏病组中表达显著低于对照组;3 个 miRNA(miR-36643p、miR-1275 和 miR-4796-3p)在先天性心脏病组中表达显著高于对照组。 结论 孕妇血清中 7 个差异表达的 miRNA 可作为胎儿先天性心脏病的无创产前诊断标志物,具有潜在的临床价值。
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顾卉  陈骊珠  薛佳  黄天楚  袁正伟
关键词:  先天性心脏病')" href="#">先天性心脏病  microRNA   产前诊断  血清标志物    
Abstract: 【Abstract】 Objective To screen the differential expressed microRNAs (miRNAs) in maternal serum of pregnant women with congenital heart disease (CHD) fetuses and to confirm the potential biomarkers for non-invasive prenatal diagnosis of CHD.  Methods From January 2012 to December 2015, 50 pregnant women who were diagnosed as pregnant with CHD fetuses by prenatal ultrasound examination in Shengjing Hospital of China Medical University were recruited. Fifty cases of normal pregnant women whose gestational week and maternal age matched with the CHD group were selected as the control group. The high-throughput screening was used for the differential expressed microRNAs in maternal serum with CHD fetuses by miRNA microarray analysis. The differential expressed microRNAsin maternal serum were further verified by the method of real-time quantitative PCR between study group and control group. Independent sample t-test and receiver operating characteristic (ROC) curves were used for statistical analysis. Results Among the 1 033 miRNAs detected in the maternal serum by miRNA microarray analysis, 38 miRNAs showed at least a 2-fold difference between study group and control
group. Bioinformatics signal pathway analysis showed that the top two pathways were adrenergic signaling
pathway and AMPK signaling pathway in cardiomyocytes. The expression of 4 miRNAs (miR-3199, miR-
125b-2-3p, miR-4666a-3p and miR-4681) in CHD group was significantly lower than that in control group;
the expression of 3 miRNAs (miR-3664-3p, miR-1275 and miR-4796-3p) in CHD group was significantly
higher than that in control group.  Conclusions  The 7 differential expressed miRNAs in maternal serum of pregnant women can be used as the new biomarkers for non-invasive prenatal diagnosis of fetal CHD and has latent clinical value.
Key words:  Congenital heart defect')" href="#">Congenital heart defect    microRNA    Prenatal diagnosis    Serum biomarker
收稿日期:  2018-03-13                出版日期:  2019-01-30      发布日期:  2019-02-01      期的出版日期:  2019-01-30
基金资助: 国家重点研发计划(2016YFC1000505);国家自然科学基金(81671469、81771595);辽宁省自然科学基金指导计划(20170541002)
通讯作者:  袁正伟http://www.sj-hospital.org/show.php?mesid=3202    E-mail:  yuanzw@hotmail.com
引用本文:    
顾卉  陈骊珠  薛佳  黄天楚  袁正伟. 先天性心脏病胎儿母体血清中的microRNA表达谱及其诊断意义[J]. 发育医学电子杂志, 2019, 7(1): 32-37.
GU hui CHEN Li-zhu XUE Jia HUANG Tian-chu YUAN Zheng-wei. microRNA expression profile in the serum of pregnant women with congenital heart disease fetuses and its diagnosis value. Journal of Developmental Medicine(Electronic Version), 2019, 7(1): 32-37.
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