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Title: Multiplexed targeted mass spectrometry assays for prostate cancer-associated urinary proteins

Abstract

Biomarkers for effective early diagnosis and prognosis of prostate cancer are still lacking. Multiplexed assays for cancer-associated proteins could be useful for identifying biomarkers for cancer detection and stratification. Herein, we report the development of sensitive targeted mass spectrometry assays for simultaneous quantification of 10 prostate cancer-associated proteins in urine. The diagnostic utility of these markers was evaluated with an initial cohort of 20 clinical urine samples. Individual marker concentration was normalized against the measured urinary prostate-specific antigen level as a reference of prostate-specific secretion. The areas under the receiver-operating characteristic curves for the 10 proteins ranged from 0.75 for CXCL14 to 0.87 for CEACAM5. Furthermore, MMP9 level was found to be significantly higher in patients with high Gleason scores, suggesting a potential of MMP9 as a marker for risk level assessment. Taken together, our work illustrated the feasibility of accurate multiplexed measurements of low-abundance cancer-associated proteins in urine and provided a viable path forward for preclinical verification of candidate biomarkers for prostate cancer.

Authors:
; ; ; ; ; ; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)
Sponsoring Org.:
USDOE
OSTI Identifier:
1439709
Report Number(s):
PNNL-SA-128413
Journal ID: ISSN 1949-2553; 48135; 453040075
DOE Contract Number:
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Oncotarget; Journal Volume: 8; Journal Issue: 60
Country of Publication:
United States
Language:
English
Subject:
Environmental Molecular Sciences Laboratory

Citation Formats

Shi, Tujin, Quek, Sue-Ing, Gao, Yuqian, Nicora, Carrie D., Nie, Song, Fillmore, Thomas L., Liu, Tao, Rodland, Karin D., Smith, Richard D., Leach, Robin J., Thompson, Ian M., Vitello, Elizabeth A., Ellis, William J., Liu, Alvin Y., and Qian, Wei-Jun. Multiplexed targeted mass spectrometry assays for prostate cancer-associated urinary proteins. United States: N. p., 2017. Web. doi:10.18632/oncotarget.21710.
Shi, Tujin, Quek, Sue-Ing, Gao, Yuqian, Nicora, Carrie D., Nie, Song, Fillmore, Thomas L., Liu, Tao, Rodland, Karin D., Smith, Richard D., Leach, Robin J., Thompson, Ian M., Vitello, Elizabeth A., Ellis, William J., Liu, Alvin Y., & Qian, Wei-Jun. Multiplexed targeted mass spectrometry assays for prostate cancer-associated urinary proteins. United States. doi:10.18632/oncotarget.21710.
Shi, Tujin, Quek, Sue-Ing, Gao, Yuqian, Nicora, Carrie D., Nie, Song, Fillmore, Thomas L., Liu, Tao, Rodland, Karin D., Smith, Richard D., Leach, Robin J., Thompson, Ian M., Vitello, Elizabeth A., Ellis, William J., Liu, Alvin Y., and Qian, Wei-Jun. Tue . "Multiplexed targeted mass spectrometry assays for prostate cancer-associated urinary proteins". United States. doi:10.18632/oncotarget.21710.
@article{osti_1439709,
title = {Multiplexed targeted mass spectrometry assays for prostate cancer-associated urinary proteins},
author = {Shi, Tujin and Quek, Sue-Ing and Gao, Yuqian and Nicora, Carrie D. and Nie, Song and Fillmore, Thomas L. and Liu, Tao and Rodland, Karin D. and Smith, Richard D. and Leach, Robin J. and Thompson, Ian M. and Vitello, Elizabeth A. and Ellis, William J. and Liu, Alvin Y. and Qian, Wei-Jun},
abstractNote = {Biomarkers for effective early diagnosis and prognosis of prostate cancer are still lacking. Multiplexed assays for cancer-associated proteins could be useful for identifying biomarkers for cancer detection and stratification. Herein, we report the development of sensitive targeted mass spectrometry assays for simultaneous quantification of 10 prostate cancer-associated proteins in urine. The diagnostic utility of these markers was evaluated with an initial cohort of 20 clinical urine samples. Individual marker concentration was normalized against the measured urinary prostate-specific antigen level as a reference of prostate-specific secretion. The areas under the receiver-operating characteristic curves for the 10 proteins ranged from 0.75 for CXCL14 to 0.87 for CEACAM5. Furthermore, MMP9 level was found to be significantly higher in patients with high Gleason scores, suggesting a potential of MMP9 as a marker for risk level assessment. Taken together, our work illustrated the feasibility of accurate multiplexed measurements of low-abundance cancer-associated proteins in urine and provided a viable path forward for preclinical verification of candidate biomarkers for prostate cancer.},
doi = {10.18632/oncotarget.21710},
journal = {Oncotarget},
number = 60,
volume = 8,
place = {United States},
year = {Tue Oct 10 00:00:00 EDT 2017},
month = {Tue Oct 10 00:00:00 EDT 2017}
}