Selected reaction monitoring approach for validating peptide biomarkers

Qing Wang, Ming Zhang, Tyler Tomita, Joshua T. Vogelstein, Shibin Zhou, Nickolas Papadopoulos, Kenneth W Kinzler, Bert Vogelstein

Research output: Contribution to journalArticle

Abstract

We here describe a selected reaction monitoring (SRM)-based approach for the discovery and validation of peptide biomarkers for cancer. The first stage of this approach is the direct identification of candidate peptides through comparison of proteolytic peptides derived from the plasma of cancer patients or healthy individuals. Several hundred candidate peptides were identified through this method, providing challenges for choosing and validating the small number of peptides that might prove diagnostically useful. To accomplish this validation, we used 2D chromatography coupled with SRM of candidate peptides. We applied this approach, called sequential analysis of fractionated eluates by SRM (SAFE-SRM), to plasma from cancer patients and discovered two peptides encoded by the peptidyl-prolyl cis-trans isomerase A (PPIA) gene whose abundance was increased in the plasma of ovarian cancer patients. At optimal thresholds, elevated levels of at least one of these two peptides was detected in 43 (68.3%) of 63 women with ovarian cancer but in none of 50 healthy controls. In addition to providing a potential biomarker for ovarian cancer, this approach is generally applicable to the discovery of peptides characteristic of various disease states.

Original languageEnglish (US)
Pages (from-to)13519-13524
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number51
DOIs
StatePublished - Dec 19 2017

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Biomarkers
Peptides
Ovarian Neoplasms
Cyclophilin A
Tumor Biomarkers
Chromatography
Neoplasms
Genes

Keywords

  • Cancer diagnostics
  • Clinical proteomics
  • Peptide biomarker
  • Plasma biomarker
  • Selected reaction monitoring

ASJC Scopus subject areas

  • General

Cite this

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title = "Selected reaction monitoring approach for validating peptide biomarkers",
abstract = "We here describe a selected reaction monitoring (SRM)-based approach for the discovery and validation of peptide biomarkers for cancer. The first stage of this approach is the direct identification of candidate peptides through comparison of proteolytic peptides derived from the plasma of cancer patients or healthy individuals. Several hundred candidate peptides were identified through this method, providing challenges for choosing and validating the small number of peptides that might prove diagnostically useful. To accomplish this validation, we used 2D chromatography coupled with SRM of candidate peptides. We applied this approach, called sequential analysis of fractionated eluates by SRM (SAFE-SRM), to plasma from cancer patients and discovered two peptides encoded by the peptidyl-prolyl cis-trans isomerase A (PPIA) gene whose abundance was increased in the plasma of ovarian cancer patients. At optimal thresholds, elevated levels of at least one of these two peptides was detected in 43 (68.3{\%}) of 63 women with ovarian cancer but in none of 50 healthy controls. In addition to providing a potential biomarker for ovarian cancer, this approach is generally applicable to the discovery of peptides characteristic of various disease states.",
keywords = "Cancer diagnostics, Clinical proteomics, Peptide biomarker, Plasma biomarker, Selected reaction monitoring",
author = "Qing Wang and Ming Zhang and Tyler Tomita and Vogelstein, {Joshua T.} and Shibin Zhou and Nickolas Papadopoulos and Kinzler, {Kenneth W} and Bert Vogelstein",
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T1 - Selected reaction monitoring approach for validating peptide biomarkers

AU - Wang, Qing

AU - Zhang, Ming

AU - Tomita, Tyler

AU - Vogelstein, Joshua T.

AU - Zhou, Shibin

AU - Papadopoulos, Nickolas

AU - Kinzler, Kenneth W

AU - Vogelstein, Bert

PY - 2017/12/19

Y1 - 2017/12/19

N2 - We here describe a selected reaction monitoring (SRM)-based approach for the discovery and validation of peptide biomarkers for cancer. The first stage of this approach is the direct identification of candidate peptides through comparison of proteolytic peptides derived from the plasma of cancer patients or healthy individuals. Several hundred candidate peptides were identified through this method, providing challenges for choosing and validating the small number of peptides that might prove diagnostically useful. To accomplish this validation, we used 2D chromatography coupled with SRM of candidate peptides. We applied this approach, called sequential analysis of fractionated eluates by SRM (SAFE-SRM), to plasma from cancer patients and discovered two peptides encoded by the peptidyl-prolyl cis-trans isomerase A (PPIA) gene whose abundance was increased in the plasma of ovarian cancer patients. At optimal thresholds, elevated levels of at least one of these two peptides was detected in 43 (68.3%) of 63 women with ovarian cancer but in none of 50 healthy controls. In addition to providing a potential biomarker for ovarian cancer, this approach is generally applicable to the discovery of peptides characteristic of various disease states.

AB - We here describe a selected reaction monitoring (SRM)-based approach for the discovery and validation of peptide biomarkers for cancer. The first stage of this approach is the direct identification of candidate peptides through comparison of proteolytic peptides derived from the plasma of cancer patients or healthy individuals. Several hundred candidate peptides were identified through this method, providing challenges for choosing and validating the small number of peptides that might prove diagnostically useful. To accomplish this validation, we used 2D chromatography coupled with SRM of candidate peptides. We applied this approach, called sequential analysis of fractionated eluates by SRM (SAFE-SRM), to plasma from cancer patients and discovered two peptides encoded by the peptidyl-prolyl cis-trans isomerase A (PPIA) gene whose abundance was increased in the plasma of ovarian cancer patients. At optimal thresholds, elevated levels of at least one of these two peptides was detected in 43 (68.3%) of 63 women with ovarian cancer but in none of 50 healthy controls. In addition to providing a potential biomarker for ovarian cancer, this approach is generally applicable to the discovery of peptides characteristic of various disease states.

KW - Cancer diagnostics

KW - Clinical proteomics

KW - Peptide biomarker

KW - Plasma biomarker

KW - Selected reaction monitoring

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