Advanced

Identification of a Novel Proteoform of Prostate Specific Antigen (SNP-L132I) in Clinical Samples by Multiple Reaction Monitoring.

Végvári, Ákos LU ; Sjödin, Karin LU ; Rezeli, Melinda LU ; Malm, Johan LU ; Lilja, Hans LU ; Laurell, Thomas LU and Marko-Varga, György LU (2013) In Molecular & Cellular Proteomics 12(10). p.2761-2773
Abstract
Prostate specific antigen (PSA) is a well-established tumor marker, which is frequently employed as model biomarker to develop and evaluate emerging quantitative proteomics techniques, partially due to wide access to commercialized immunoassays serving as "gold standard". We designed a multiple reaction monitoring (MRM) assay to detect PSA proteoforms in clinical samples (n=72), utilizing specificity and sensitivity of the method. We report for the first time, a PSA proteoform, coded by SNP-L132I (rs2003783), observed in 9 samples in both heterozygous (n=7) and homozygous (n=2) expression profiles. Other isoforms of PSA, derived from protein databases, were not identified by four unique proteotypic tryptic peptides. We have also utilized... (More)
Prostate specific antigen (PSA) is a well-established tumor marker, which is frequently employed as model biomarker to develop and evaluate emerging quantitative proteomics techniques, partially due to wide access to commercialized immunoassays serving as "gold standard". We designed a multiple reaction monitoring (MRM) assay to detect PSA proteoforms in clinical samples (n=72), utilizing specificity and sensitivity of the method. We report for the first time, a PSA proteoform, coded by SNP-L132I (rs2003783), observed in 9 samples in both heterozygous (n=7) and homozygous (n=2) expression profiles. Other isoforms of PSA, derived from protein databases, were not identified by four unique proteotypic tryptic peptides. We have also utilized our MRM assay for precise quantitative analysis of PSA concentrations in both seminal and blood plasma samples. The analytical performance was evaluated, providing close agreement between each quantitation based on three selected peptides (LSEPAELTDAVK, IVGGWECEK and SVILLGR) and a routinely used commercialized immunoassay. Additionally, we have disclosed that the peptide IVGGWECEK is shared with kallikrein-related peptidase 2 and therefore not unique for PSA. Hence, we propose to use another tryptic sequence (SVILLGR) for accurate MRM-quantification of PSA in clinical samples. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular & Cellular Proteomics
volume
12
issue
10
pages
2761 - 2773
publisher
American Society for Biochemistry and Molecular Biology
external identifiers
  • pmid:23842001
  • wos:000330537000008
  • scopus:84885092136
ISSN
1535-9484
DOI
10.1074/mcp.M113.028365
language
English
LU publication?
yes
id
e5abc9b9-890d-4288-bca3-1bc2f5b8917d (old id 3955991)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23842001?dopt=Abstract
date added to LUP
2013-08-02 11:58:50
date last changed
2019-10-01 01:07:40
@article{e5abc9b9-890d-4288-bca3-1bc2f5b8917d,
  abstract     = {Prostate specific antigen (PSA) is a well-established tumor marker, which is frequently employed as model biomarker to develop and evaluate emerging quantitative proteomics techniques, partially due to wide access to commercialized immunoassays serving as "gold standard". We designed a multiple reaction monitoring (MRM) assay to detect PSA proteoforms in clinical samples (n=72), utilizing specificity and sensitivity of the method. We report for the first time, a PSA proteoform, coded by SNP-L132I (rs2003783), observed in 9 samples in both heterozygous (n=7) and homozygous (n=2) expression profiles. Other isoforms of PSA, derived from protein databases, were not identified by four unique proteotypic tryptic peptides. We have also utilized our MRM assay for precise quantitative analysis of PSA concentrations in both seminal and blood plasma samples. The analytical performance was evaluated, providing close agreement between each quantitation based on three selected peptides (LSEPAELTDAVK, IVGGWECEK and SVILLGR) and a routinely used commercialized immunoassay. Additionally, we have disclosed that the peptide IVGGWECEK is shared with kallikrein-related peptidase 2 and therefore not unique for PSA. Hence, we propose to use another tryptic sequence (SVILLGR) for accurate MRM-quantification of PSA in clinical samples.},
  author       = {Végvári, Ákos and Sjödin, Karin and Rezeli, Melinda and Malm, Johan and Lilja, Hans and Laurell, Thomas and Marko-Varga, György},
  issn         = {1535-9484},
  language     = {eng},
  number       = {10},
  pages        = {2761--2773},
  publisher    = {American Society for Biochemistry and Molecular Biology},
  series       = {Molecular & Cellular Proteomics},
  title        = {Identification of a Novel Proteoform of Prostate Specific Antigen (SNP-L132I) in Clinical Samples by Multiple Reaction Monitoring.},
  url          = {http://dx.doi.org/10.1074/mcp.M113.028365},
  volume       = {12},
  year         = {2013},
}