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

被引：30

作者：

Cho, Chan-Kyung J. ^{[2
]}

Drabovich, Andrei P.

Batruch, Ihor ^{[3
]}

Diamandis, Eleftherios P. ^{[1
,2
,3
]}

机构：

[1] Mt Sinai Hosp, Dept Pathol & Lab Med, Samuel Lunenfeld Res Inst, Toronto, ON M57 3L9, Canada

[2] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada

[3] Univ Hlth Network, Dept Clin Biochem, Toronto, ON, Canada

来源：

JOURNAL OF PROTEOMICS | 2011年 / 74卷 / 10期

基金：

加拿大健康研究院; 加拿大自然科学与工程研究理事会;

关键词：

Biomarker; Down syndrome; Prenatal screening; GEL; MMP2; MUC13; DPP4; CPA1; CELL-SURFACE MUCIN; PROTEOME ANALYSIS; EXPRESSION; MUC13; IDENTIFICATION; DIAGNOSIS; RECEPTOR; LESIONS;

D O I：

10.1016/j.jprot.2011.05.025

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2011 Elsevier B.V. All rights reserved.

引用

页码：2052 / 2059

页数：8

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