Detection of candidate biomarkers of prostate cancer progression in serum: a depletion-free 3D LC/MS quantitative proteomics pilot study

Br J Cancer. 2016 Oct 25;115(9):1078-1086. doi: 10.1038/bjc.2016.291. Epub 2016 Sep 29.

Abstract

Background: Prostate cancer (PCa) is the most common male cancer in the United Kingdom and we aimed to identify clinically relevant biomarkers corresponding to stage progression of the disease.

Methods: We used enhanced proteomic profiling of PCa progression using iTRAQ 3D LC mass spectrometry on high-quality serum samples to identify biomarkers of PCa.

Results: We identified >1000 proteins. Following specific inclusion/exclusion criteria we targeted seven proteins of which two were validated by ELISA and six potentially interacted forming an 'interactome' with only a single protein linking each marker. This network also includes accepted cancer markers, such as TNF, STAT3, NF-κB and IL6.

Conclusions: Our linked and interrelated biomarker network highlights the potential utility of six of our seven markers as a panel for diagnosing PCa and, critically, in determining the stage of the disease. Our validation analysis of the MS-identified proteins found that SAA alongside KLK3 may improve categorisation of PCa than by KLK3 alone, and that TSR1, although not significant in this model, might also be a clinically relevant biomarker.

MeSH terms

  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / metabolism*
  • Blood Chemical Analysis / methods
  • Chromatography, Liquid
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Male
  • Pilot Projects
  • Prognosis
  • Prostatic Neoplasms / blood*
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / pathology*
  • Proteomics / methods*
  • Reproducibility of Results
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization*

Substances

  • Biomarkers, Tumor