Expression profile of maternal circulating microRNAs as non-invasive biomarkers for prenatal diagnosis of congenital heart defects

Expression profile of maternal circulating microRNAs as non-invasive biomarkers for prenatal diagnosis of congenital heart defects
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母体循环 microRNA 的表达谱作为先天性心脏病产前诊断的非侵入性生物标志物

DOI:
10.1016/j.biopha.2018.10.110
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发表时间:
2019-01-01
影响因子:
7.5
通讯作者:
Yuan, Zhengwei
Yuan, Zhengwei
中科院分区:
医学2区
文献类型:
--
作者:
Gu, Hui;Chen, Lizhu;Yuan, Zhengwei

文献摘要

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目的:母体循环中无细胞胎儿microRNAs(miRNAs)的发现为非侵入性产前诊断开辟了新的可能性。本研究旨在探讨胎儿先天性心脏病(CHD)孕妇血清中循环miRNA作为潜在生物标志物的意义。miRNA微阵列和实时荧光定量PCR检测miRNA的表达。结果:38个miRNA在CHD组和对照组血清中差异表达。其中,9个下调和3个上调的miRNA通过实时PCR验证。与分娩前相比,这些miRNAs中的10种在分娩后的正常母体血清中迅速减少。特别地,我们鉴定了由四种miRNAs组成的生物标志物组,(miR-142- 5 p、miR-1275、miR-4666 a-3 p和miR-3664- 3 p)能够区分CHD与对照(ROC曲线下面积(AUC),0.920; p < 0.0001)。这些异常妊娠相关miRNAs在母体血清中的发现可能是胎儿CHD非侵入性产前诊断的潜在生物标志物。
Objective: The discovery of cell free fetal microRNAs (miRNAs) in maternal circulation has opened up novel probabilities for non-invasive prenatal diagnosis. This study aims to investigate circulating miRNAs as potential biomarkers in the serum of pregnant women with congenital heart defect (CHD) fetuses.Method: A total of 110 pregnant women including 50 CHD cases and 60 healthy controls were included in this study. miRNA microarray followed by real-time PCR was used to explore miRNA expression. Receiver operating characteristic (ROC) curves were calculated to assess the diagnostic capability of miRNAs for fetal CHDs.Results: 38 Serum miRNAs were revealed to be differentially expressed in the CHD group as compared to control group via microarray. Among these, nine down-regulated and three up-regulated miRNAs were validated by real-time PCR. Ten of these miRNAs were rapidly reduced in the normal maternal serum after delivery as compared to before delivery. In particular, we identified a biomarker panel consisting of four miRNAs (miR-142-5p, miR-1275, miR-4666a-3p and miR-3664-3p) capable of distinguishing CHDs from controls (area under the ROC curve (AUC), 0.920; p < 0.0001).Conclusion: The discovery of these dysregulated pregnancy-associated miRNAs in maternal serum may be potential biomarkers for non-invasive prenatal diagnosis of fetal CHDs.