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

被引:26
作者
Chen, Lizhu [1 ,2 ]
Gu, Hui [1 ]
Li, Jun [3 ]
Yang, Ze-Yu [2 ]
Sun, Xiao [4 ]
Zhang, Li [5 ]
Shan, Liping [6 ]
Wu, Lina [7 ]
Wei, Xiaowei [1 ]
Zhao, Yili [8 ]
Ma, Wei [1 ]
Zhang, Henan [1 ]
Cao, Songying [1 ]
Huang, Tianchu [1 ]
Miao, Jianing [1 ]
Yuan, Zhengwei [1 ]
机构
[1] China Med Univ, Shengjing Hosp, Key Lab Hlth Minist Congenital Malformat, Shenyang 110004, Peoples R China
[2] China Med Univ, Shengjing Hosp, Dept Ultrasound, Shenyang 110004, Peoples R China
[3] China Med Univ, Shengjing Hosp, Dept Gynaecol & Obstet, Shenyang 110004, Peoples R China
[4] Shenyang Womens & Childrens Hosp, Dept Obstet & Gynaecol, Shenyang, Peoples R China
[5] Shenyang Women & Children Hlth Care Ctr, Dept Genet, Shenyang, Peoples R China
[6] China Med Univ, Shengjing Hosp, Dept Urol Surg, Shenyang 110004, Peoples R China
[7] China Med Univ, Shengjing Hosp, Dept Lab Med, Shenyang 110004, Peoples R China
[8] Eastern Virginia Med Sch, Dept Obstet & Gynecol, Norfolk, VA 23507 USA
关键词
LAMIN-A/C; VERIFICATION; MARKERS; EXPRESSION; DISCOVERY; NUCLEAR; DISEASE; PREGNANCY; PIPELINE;
D O I
10.1038/srep19248
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
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 noninvasive 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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页数:10
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