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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\u20130.88]. 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.<\/jats:p>","DOI":"10.1038\/srep17559","type":"journal-article","created":{"date-parts":[[2015,12,22]],"date-time":"2015-12-22T10:33:39Z","timestamp":1450780419000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Identification of PCSK9 as a novel serum biomarker for the prenatal diagnosis of neural tube defects using iTRAQ quantitative proteomics"],"prefix":"10.1038","volume":"5","author":[{"given":"Dong","family":"An","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianchu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guifeng","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weilin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songying","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengwei","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,12,22]]},"reference":[{"key":"BFsrep17559_CR1","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1002\/bdra.23082","volume":"94","author":"AM Molloy","year":"2012","unstructured":"Molloy, A. 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