Comprehensive maternal serum proteomics identifies the cytoskeletal proteins as non-invasive biomarkers in prenatal diagnosis of congenital heart defects

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作者
Lizhu Chen
Hui Gu
Jun Li
Ze-Yu Yang
Xiao Sun
Li Zhang
Liping Shan
Lina Wu
Xiaowei Wei
Yili Zhao
Wei Ma
Henan Zhang
Songying Cao
Tianchu Huang
Jianing Miao
Zhengwei Yuan
机构
[1] Key Laboratory of Health Ministry for Congenital Malformation,Department of Ultrasound
[2] Shengjing Hospital,Department of gynaecology and obstetrics
[3] China Medical University,Department of gynaecology and obstetrics
[4] Shengjing Hospital,Department of genetics
[5] China Medical University,Department of Urologic Surgery
[6] Shengjing Hospital,Department of Laboratory Medicine
[7] China Medical University,Department of Obstetrics and Gynecology
[8] Shenyang women’s and children’s Hospital,undefined
[9] Shenyang Women and Children Health Care Centre,undefined
[10] Shengjing Hospital,undefined
[11] China Medical University,undefined
[12] Shengjing Hospital,undefined
[13] China Medical University,undefined
[14] Eastern Virginia Medical School,undefined
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摘要
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.
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