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Differential exoprotease activities confer tumor-specific serum peptidome patterns

Villanueva, Josep ; Shaffer, David R ; Philip, John ; Chaparro, Carlos A ; Erdjument-Bromage, Hediye ; Olshen, Adam B ; Fleisher, Martin ; Lilja, Hans LU ; Brogi, Edi and Boyd, Jeff , et al. (2006) In Journal of Clinical Investigation 116(1). p.271-284
Abstract
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Investigation
volume
116
issue
1
pages
271 - 284
publisher
Am Soc Clin Investig
external identifiers
  • pmid:16395409
  • scopus:31044436630
ISSN
0021-9738
DOI
10.1172/JCI26022
language
English
LU publication?
yes
id
f8e4375f-9ec3-4f88-b4b1-7d5ad769345a (old id 1136364)
date added to LUP
2016-04-01 17:02:50
date last changed
2020-12-29 01:31:38
@article{f8e4375f-9ec3-4f88-b4b1-7d5ad769345a,
  abstract     = {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.},
  author       = {Villanueva, Josep and Shaffer, David R and Philip, John and Chaparro, Carlos A and Erdjument-Bromage, Hediye and Olshen, Adam B and Fleisher, Martin and Lilja, Hans and Brogi, Edi and Boyd, Jeff and Sanchez-Carbayo, Marta and Holland, Eric C and Cordon-Cardo, Carlos and Scher, Howar},
  issn         = {0021-9738},
  language     = {eng},
  number       = {1},
  pages        = {271--284},
  publisher    = {Am Soc Clin Investig},
  series       = {Journal of Clinical Investigation},
  title        = {Differential exoprotease activities confer tumor-specific serum peptidome patterns},
  url          = {http://dx.doi.org/10.1172/JCI26022},
  doi          = {10.1172/JCI26022},
  volume       = {116},
  year         = {2006},
}