Comprehensive maternal serum proteomics identifies the cytoskeletal proteins as non-invasive biomarkers in prenatal diagnosis of congenital heart defects.
Comprehensive maternal serum proteomics identifies the cytoskeletal proteins as non-invasive biomarkers in prenatal diagnosis of congenital heart defects.
复制标题
综合母体血清蛋白质组学将细胞骨架蛋白鉴定为先天性心脏病产前诊断中的非侵入性生物标志物
DOI：
10.1038/srep19248
复制
发表时间：
2016-01-11
影响因子：
4.6
通讯作者：
Yuan Z
中科院分区：
文献类型：
--
作者：
Chen L;Gu H;Li J;Yang ZY;Sun X;Zhang L;Shan L;Wu L;Wei X;Zhao Y;Ma W;Zhang H;Cao S;Huang T;Miao J;Yuan Z
先天性心脏病（CHD）是最常见的一组主要出生缺陷。目前还没有临床上用于产前检测CHD的生物标志物。在这里，我们进行了一个全面的母亲血清蛋白质组学评估，结合免疫测定，为发现非侵入性的生物标志物产前诊断冠心病。共有370名女性被纳入本研究。首先使用相对和绝对定量（iTRAQ）蛋白质组学方法的同量异序标记，比较收集自患有CHD或正常胎儿的妇女的合并血清中的蛋白质谱，47种蛋白质显示出显着的差异表达。使用多反应监测质谱法（MRM-MS）对11种蛋白质进行靶向验证，然后使用ELISA分析进一步验证所得候选生物标志物。最后，我们确定了一个由4种细胞骨架蛋白组成的生物标志物组，能够区分CHD妊娠和正常妊娠[受试者工作特征曲线下面积（AUC）为0.938，P < 0.0001]。母血清中细胞骨架蛋白变化的发现不仅有助于CHD的产前诊断，而且可能为CHD胚胎发生的研究提供新的思路。
Congenital heart defects (CHDs) are the most common group of major birth defects. Presently there are no clinically used biomarkers for prenatally detecting CHDs. Here, we performed a comprehensive maternal serum proteomics assessment, combined with immunoassays, for the discovery of non-invasive biomarkers for prenatal diagnosis of CHDs. A total of 370 women were included in this study. An isobaric tagging for relative and absolute quantification (iTRAQ) proteomic approach was used first to compare protein profiles in pooled serum collected from women who had CHD-possessing or normal fetuses and 47 proteins displayed significant differential expressions. Targeted verifications were performed on 11 proteins using multiple reaction monitoring mass spectrometry (MRM-MS) and the resultant candidate biomarkers were then further validated using ELISA analysis. Finally, we identified a biomarker panel composed of 4 cytoskeletal proteins capable of differentiating CHD-pregnancies from normal ones [with an area under the receiver operating characteristic curve (AUC) of 0.938, P < 0.0001]. The discovery of cytoskeletal protein changes in maternal serum not only could help us in prenatal diagnosis of CHDs, but also may shed new light on CHD embryogenesis studies.