The urinary peptidome as a noninvasive biomarker development strategy for prenatal screening of Down's syndrome

Author Identifier

wei wang

https://orcid.org/0000-0002-1430-1360

Document Type

Journal Article

Publication Title

OMICS : A Journal of Integrative Biology

ISSN

1557-8100

Volume

23

Issue

9

First Page

439

Last Page

447

PubMed ID

31381471

Publisher

Mary Ann Liebert

School

School of Medical and Health Sciences

RAS ID

30044

Funders

National Natural Science Foundation of China (Grant Numbers: 51673119, 81773527, 81273170, 81370083, and 81573215)

Australia-China International Collaborative Grant (NHMRC APP1112767 - NSFC 81561128020).

China Scholarship Council (CSC Number: 201708110200).

Grant Number

NHMRC Number : 1112767

Comments

Shan, D., Wang, H., Khatri, P., Niu, Y., Song, W., Zhao, S., ... Yin, C. (2019). The urinary peptidome as a noninvasive biomarker development strategy for prenatal screening of Down's syndrome. Omics: A Journal of Integrative Biology, 23(9), 439-447. Available here

Abstract

Prenatal screening for Down's syndrome based on maternal age, ultrasound measures, and maternal serum biomarkers is recommended worldwide, but the false-positive rate and poor diagnostic performance of these screening tests remain problematic. Genetic analysis of cell-free DNA in maternal blood has been developed as a new prenatal screening for Down's syndrome, but it has a number of limitations, including turnaround time and cost. Prenatal screening diagnostic innovation calls for new tests that are noninvasive, accurate, and affordable. We report original observations on potential peptide biomarkers in maternal urine for screening of fetal Down's syndrome. The peptidome of urine samples from 23 pregnant women carrying Down's syndrome fetuses and 30 pregnant women carrying fetuses with normal karyotype was fractionated by weak cation exchange magnetic beads and analyzed by MALDI-TOF mass spectrometry. Levels of six peptides (m/z 1022.1, 1032.1, 1099.5, 1155.9, 1306.6, and 2365.6) were significantly altered between the case and control groups after controlling for maternal and gestational age. A classification model was constructed based on these candidate peptides that could differentiate fetuses with Down's syndrome from controls with a sensitivity of 95.7%, a specificity of 70.0%, and an area under receiver operating characteristic curves of 0.909 (95% confidence interval, 0.835–0.984). Peptide peaks at m/z 1099.5 and 1155.9 were identified as the partial sequences of alpha-1-antitrypsin and heat shock protein beta-1, respectively. These new findings support the new idea that maternal urinary peptidome offers prospects for noninvasive biomarker discovery and development for the prenatal screening of fetal Down's syndrome.

DOI

10.1089/omi.2019.0098

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