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Differential exoprotease activities confer tumor-specific serum peptidome patterns

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Author

  • Josep Villanueva
  • David R Shaffer
  • John Philip
  • Carlos A Chaparro
  • Hediye Erdjument-Bromage
  • Adam B Olshen
  • Martin Fleisher
  • Hans Lilja
  • Edi Brogi
  • Jeff Boyd
  • Marta Sanchez-Carbayo
  • Eric C Holland
  • Carlos Cordon-Cardo
  • Howar Scher
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Summary, in English

Recent studies have established distinctive serum polypeptide patterns through mass spectrometry (MS) that reportedly correlate with clinically relevant outcomes. Wider acceptance of these signatures as valid biomarkers for disease may follow sequence characterization of the components and elucidation of the mechanisms by which they are generated. Using a highly optimized peptide extraction and matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) MS-based approach, we now show that a limited subset of serum peptides (a signature) provides accurate class discrimination between patients with 3 types of solid tumors and controls without cancer. Targeted sequence identification of 61 signature peptides revealed that they fall into several tight clusters and that most are generated by exopeptidase activities that confer cancer type-specific differences superimposed on the proteolytic events of the ex vivo coagulation and complement degradation pathways. This small but robust set of marker peptides then enabled highly accurate class prediction for an external validation set of prostate cancer samples. In sum, this study provides a direct link between peptide marker profiles of disease and differential protease activity, and the patterns we describe may have clinical utility as surrogate markers for detection and classification of cancer. Our findings also have important implications for future peptide biomarker discovery efforts.

Publishing year

2006

Language

English

Pages

271-284

Publication/Series

Journal of Clinical Investigation

Volume

116

Issue

1

Document type

Journal article

Publisher

The American Society for Clinical Investigation

Topic

  • Medicinal Chemistry

Status

Published

Research group

  • Clinical Chemistry, Malmö

ISBN/ISSN/Other

  • ISSN: 0021-9738