Development of a Multiplex Selected Reaction Monitoring Assay for Quantification of Biochemical Markers of Down Syndrome in Amniotic Fluid Samples
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- 作者：Eduardo Mart铆nez-Morillo ; Chan-Kyung J. Cho ; Andrei P. Drabovich ; Julie L.V. Shaw ; Antoninus Soosaipillai ; Eleftherios P. Diamandis
- 刊名：Journal of Proteome Research
- 出版年：2012
- 出版时间：July 6, 2012
- 年：2012
- 卷：11
- 期：7
- 页码：3880-3887
- 全文大小：328K
- 年卷期：v.11,no.7(July 6, 2012)
- ISSN：1535-3907
文摘
Down syndrome (DS) is one of the most common chromosomal abnormalities affecting about 1 of every 700 fetuses. Current screening strategies have detection rates of 90鈥?5% at a 5% false positive rate. The aim of this study was to discover new biomarkers of DS in amniotic fluid by using a multiplex selected reaction monitoring assay. Nine proteins were analyzed: CEL, CPA1, MUC13, CLCA1, MUC5AC, PLUNC, and HAPLN1, and CGB as positive control and serotransferrin as negative control. One proteotypic peptide for each protein was selected, and internal heavy isotope-labeled peptide standards were spiked into the samples. Fifty-four samples from pregnant women carrying normal (n = 37) or DS-affected (n = 17) fetuses were analyzed. The median protein concentrations for DS and normal samples, respectively, were as follows: 20 and 49 ng/mL (p < 0.01) for CEL; 3.7 and 14 ng/mL (p < 0.001) for CPA1; 80 and 263 ng/mL (p < 0.001) for MUC13; 46 and 135 ng/mL (p < 0.001) for CLCA1; 0.65 and 0.93 渭g/mL (p < 0.05) for MUC5AC; 61 and 73 ng/mL (p > 0.05) for PLUNC; 144 and 86 ng/mL (p < 0.01) for HAPLN1; 0.89 and 0.54 渭g/mL (p = 0.05) for CGB; 91 and 87 渭g/mL (p > 0.05) for serotransferrin. Statistically significant differences were found in six out of the seven candidate proteins analyzed, reflecting a different regulation in DS.