Verification of a biomarker discovery approach for detection of Down syndrome in amniotic fluid via multiplex selected reaction monitoring (SRM) assay.

Abstract:

:Prenatal screening test for Down syndrome (DS) can be improved by discovery of novel biomarkers. A multiplex selected reaction monitoring (SRM) assay was developed to test previously identified thirteen candidate proteins in amniotic fluid (AF). One unique peptide was selected for each protein based on discovery data, while three MS/MS transitions were selected based on intelligent SRM results. For one of the candidates, matrix metalloproteinase-2 (MMP2), ELISA was also performed to validate SRM results in AF and to test serum samples. Comparison of AF samples from DS versus controls via SRM assay revealed five proteins that were differentially expressed. Bile salt-activated lipase, mucin-13, carboxypeptidase A1, and dipeptidyl peptidase 4 showed a decrease in DS-affected AF, and MMP2 showed an increase, in comparison to controls (P<0.05). Discovery-based spectral counting ratios and SRM ratios showed a strong correlation, and MMP2 ELISA further confirmed the validity of the SRM data. Potential implications of differentially expressed proteins during fetal development are proposed. Our data also shows that SRM can provide a high-throughput and accurate platform for biomarker verification.

journal_name

J Proteomics

journal_title

Journal of proteomics

authors

Cho CK,Drabovich AP,Batruch I,Diamandis EP

doi

10.1016/j.jprot.2011.05.025

subject

Has Abstract

pub_date

2011-09-06 00:00:00

pages

2052-9

issue

10

eissn

1874-3919

issn

1876-7737

pii

S1874-3919(11)00216-8

journal_volume

74

pub_type

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