title: Comprehensive maternal serum proteomics identifies the cytoskeletal proteins as non-invasive biomarkers in prenatal diagnosis of congenital heart defects.
abstract: 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.
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang 110004, China.|Department of Ultrasound, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Lizhu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang 110004, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Gu
authors.affiliation: Department of gynaecology and obstetrics, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Ultrasound, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Ze-Yu
authors.initials: ZY
authors.lastname: Yang
authors.affiliation: Department of gynaecology and obstetrics, Shenyang women's and children's Hospital, Shenyang, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of genetics, Shenyang Women and Children Health Care Centre, Shenyang, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Urologic Surgery, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Shan
authors.affiliation: Department of Laboratory Medicine, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Wu
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang 110004, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk 23507, USA.
authors.forename: Yili
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang 110004, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ma
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang 110004, China.
authors.forename: Henan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang 110004, China.
authors.forename: Songying
authors.initials: S
authors.lastname: Cao
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang 110004, China.
authors.forename: Tianchu
authors.initials: T
authors.lastname: Huang
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang 110004, China.
authors.forename: Jianing
authors.initials: J
authors.lastname: Miao
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang 110004, China.
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D000328:Adult; D015415:Biomarkers; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D003598:Cytoskeletal Proteins / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006330:Heart Defects, Congenital / Q000175:diagnosis*; D006801:Humans; D034904:Lamin Type A / Q000097:blood / Q000378:metabolism; D011247:Pregnancy; D011296:Prenatal Diagnosis; D020543:Proteome; D040901:Proteomics / Q000379:methods; D012372:ROC Curve; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization; D055815:Young Adult
chemical_list: D015415:Biomarkers; D003598:Cytoskeletal Proteins; C494847:LMNA protein, human; D034904:Lamin Type A; D020543:Proteome