Multiplexed quantification of 63 proteins in human urine by multiple reaction monitoring-based mass spectrometry for discovery of potential bladder cancer biomarkers

Yi Ting Chen, Hsiao Wei Chen, Dominik Domanski, Derek S. Smith, Kung Hao Liang, Chih Ching Wu, Chien Lun Chen, Ting Chung, Min Chi Chen, Yu Sun Chang, Carol E. Parker, Christoph H. Borchers, Jau Song Yu

Research output: Contribution to journalArticlepeer-review

121 Citations (Scopus)

Abstract

Three common urological diseases are bladder cancer, urinary tract infection, and hematuria. Seventeen bladder cancer biomarkers were previously discovered using iTRAQ - these findings were verified by MRM-MS in this current study. Urine samples from 156 patients with hernia (n = 57, control), bladder cancer (n = 76), or urinary tract infection/hematuria (n = 23) were collected and subjected to multiplexed LC-MRM/MS to determine the concentrations of 63 proteins that are normally considered to be plasma proteins, but which include proteins found in our earlier iTRAQ study. Sixty-five stable isotope-labeled standard proteotypic peptides were used as internal standards for 63 targeted proteins. Twelve proteins showed higher concentrations in the bladder cancer group than in the hernia and the urinary tract infection/hematuria groups, and thus represent potential urinary biomarkers for detection of bladder cancer. Prothrombin had the highest AUC (0.796), with 71.1% sensitivity and 75.0% specificity for differentiating bladder cancer (n = 76) from non-cancerous (n = 80) patients. The multiplexed MRM-MS data was used to generate a six-peptide marker panel. This six-peptide panel (afamin, adiponectin, complement C4 gamma chain, apolipoprotein A-II precursor, ceruloplasmin, and prothrombin) can discriminate bladder cancer subjects from non-cancerous subjects with an AUC of 0.814, with a 76.3% positive predictive value, and a 77.5% negative predictive value. This article is part of a Special Section entitled: Understanding genome regulation and genetic diversity by mass spectrometry.

Original languageEnglish
Pages (from-to)3529-3545
Number of pages17
JournalJournal of Proteomics
Volume75
Issue number12
DOIs
Publication statusPublished - 27 Jun 2012
Externally publishedYes

Keywords

  • Biomarker verification
  • Bladder cancer
  • Multiple reaction monitoring
  • Multiplexed quantitation
  • Urinary proteome
  • Urinary tract infection/hematuria

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