title: Identification of PCSK9 as a novel serum biomarker for the prenatal diagnosis of neural tube defects using iTRAQ quantitative proteomics.
abstract: To identify candidate serum molecule biomarkers for the non-invasive early prenatal diagnosis of neural tube defects (NTDs), we employed an iTRAQ-based quantitative proteomic approach to analyze the proteomic changes in serum samples from embryonic day (E) 11 and E13 pregnant rats with spina bifida aperta (SBA) induced by all-trans retinoic acid. Among the 390 proteins identified, 40 proteins at E11 and 26 proteins at E13 displayed significant differential expression in the SBA groups. We confirmed 5 candidate proteins by ELISA. We observed the space-time expression changes of proprotein convertase subtilisin/kexin type 9 (PCSK9) at different stages of fetal development, including a marked decrease in the sera of NTD pregnancies and gradual increase in the sera of normal pregnancies with embryonic development. PCSK9 demonstrated the diagnostic efficacy of potential NTD biomarkers [with an area under the receiver operating characteristic curve of 0.763, 95% CI: 065-0.88]. Additionally, PCSK9 expression in the spinal cords and placentas of SBA rat fetuses was markedly decreased. PCSK9 could serve as a novel molecular biomarker for the non-invasive prenatal screening of NTDs and may be involved in the pathogenesis of NTDs at critical periods of fetal development.
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, 110004, China.|Department of Pediatrics,The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Dong
authors.initials: D
authors.lastname: An
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: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, 110004, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
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: 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: Guifeng
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, 110004, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Pediatric Surgery, Shengjing Hospital, China Medical University, Shenyang, 110004, China.
authors.forename: Weilin
authors.initials: W
authors.lastname: Wang
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, 110004, 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: 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: Zhengwei
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood; D004622:Embryo, Mammalian / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005333:Fetus / Q000378:metabolism / Q000473:pathology; D063990:Gene Ontology; D007553:Isotope Labeling / Q000379:methods*; D058977:Molecular Sequence Annotation; D009436:Neural Tube Defects / Q000097:blood* / Q000175:diagnosis*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000097:blood*; D040901:Proteomics / Q000379:methods*; D051381:Rats; D015203:Reproducibility of Results; D012697:Serine Endopeptidases / Q000097:blood*; D016137:Spina Bifida Cystica / Q000097:blood
chemical_list: D015415:Biomarkers; C472125:PCSK9 protein, human; C510804:PCSK9 protein, rat; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases