Development of a Targeted Urine Proteome Assay for kidney diseases

被引：16

作者：

Cantley, Lloyd G. ^{[1
]}

Colangelo, Christopher M. ^{[2
]}

Stone, Kathryn L. ^{[3
]}

Chung, Lisa ^{[3
]}

Belcher, Justin ^{[1
]}

Abbott, Thomas ^{[3
]}

Cantley, Jennifer L. ^{[1
]}

Williams, Kenneth R. ^{[3
,4
]}

Parikh, Chirag R. ^{[1
,5
]}

机构：

[1] Yale Univ, Dept Internal Med, Sch Med, New Haven, CT 06520 USA

[2] Primary Ion, Old Lyme, CT USA

[3] Yale Univ, WM Keck Fdn Biotechnol Lab, Sch Med, New Haven, CT 06520 USA

[4] Yale Univ, Dept Mol Biophys & Biochem, Sch Med, New Haven, CT 06520 USA

[5] Yale Univ, Program Appl Translat Res, Sch Med, New Haven, CT 06520 USA

来源：

PROTEOMICS CLINICAL APPLICATIONS | 2016年 / 10卷 / 01期

关键词：

Chronic kidney disease; Polycystic kidney disease; Targeted proteomics; Urine; MASS-SPECTROMETER; CARDIOVASCULAR-DISEASE; HUMAN PLASMA; PROTEINS; BIOMARKERS; QUANTITATION; PIPELINE; ELECTROPHORESIS; QUANTIFICATION; IDENTIFICATION;

D O I：

10.1002/prca.201500020

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

PurposeSince human urine is the most readily available biofluid whose proteome changes in response to disease, it is a logical sample for identifying protein biomarkers for kidney diseases. Experimental designPotential biomarkers were identified by using a multiproteomics workflow to compare urine proteomes of kidney transplant patients with immediate and delayed graft function. Differentially expressed proteins were identified, and corresponding stable isotope labeled internal peptide standards were synthesized for scheduled MRM. ResultsThe Targeted Urine Proteome Assay (TUPA) was then developed by identifying those peptides for which there were at least two transitions for which interference in a urine matrix across 156 MRM runs was <30%. This resulted in an assay that monitors 224 peptides from 167 quantifiable proteins. Conclusions and clinical relevanceTUPA opens the way for using a robust mass spectrometric technology, MRM, for quantifying and validating biomarkers from among 167 urinary proteins. This approach, while developed using differentially expressed urinary proteins from patients with delayed versus immediate graft function after kidney transplant, can be expanded to include differentially expressed urinary proteins in multiple kidney diseases. Thus, TUPA could provide a single assay to help diagnose, prognose, and manage many kidney diseases.

引用

页码：58 / 74

页数：17

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