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Proteomics Clin Appl. 2019 Jul;13(4):e1700111. doi: 10.1002/prca.201700111. Epub 2019 Jan 28.

Multiplexed LC-ESI-MRM-MS-based Assay for Identification of Coronary Artery Disease Biomarkers in Human Plasma.

Author information

1
Molecular You Corporation, Vancouver, British Columbia, Canada.
2
NCE CECR PROOF Centre of Excellence, Vancouver, British Columbia, Canada.
3
The UVic-Genome BC Proteomics Centre, University of Victoria, Victoria, British Columbia, Canada.
4
Providence Heart and Lung Institute and the James Hogg Research Center, St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
5
Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
6
Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada.
7
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
8
Department of Statistics, University of British Columbia, Vancouver, British Columbia, Canada.

Abstract

PURPOSE:

A highly-multiplexed LC-ESI-multiple reaction monitoring-MS-based assay is developed for the identification of coronary artery disease (CAD) biomarkers in human plasma.

EXPERIMENTAL DESIGN:

The assay is used to measure 107 stable isotope labeled peptide standards and native peptides from 64 putative biomarkers of cardiovascular diseases in tryptic digests of plasma from subjects with (n = 70) and without (n = 45) angiographic evidence of CAD and no subsequent cardiovascular mortality during follow-up.

RESULTS:

Extensive computational and statistical analysis reveals six plasma proteins associated with CAD, namely apolipoprotein CII, C reactive protein, CD5 antigen-like, fibronectin, inter alpha trypsin inhibitor heavy chain H1, and protein S. The identified proteins are combined into a LASSO-logistic score with high classification performance (cross-validated area under the curve = 0.74). When combined with a separate score computed from markers currently used in the clinic with similar performance, the area under the receiver operating curve increases to 0.84. Similar results are observed in an independent set of subjects (n = 87).

CONCLUSIONS AND CLINICAL RELEVANCE:

If externally validated, the assay and identified biomarkers can improve CAD risk stratification.

KEYWORDS:

MRM-MS; biomarkers; classification; coronary artery disease; proteomics

PMID:
30632678
DOI:
10.1002/prca.201700111

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