Analysis of the Plasma Peptidome from Pancreas Cancer Patients Connects a Peptide in Plasma to Overexpression of the Parent Protein in Tumors

Blood circulates through nearly every organ including tumors. Therefore, plasma is a logical source to search for tumor-derived proteins and peptides. The challenge with plasma is that it is a complex bodily fluid composed of high concentrations of normal host proteins that obscure identification of...

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Bibliographic Details
Published in:Journal of proteome research 2009-10, Vol.8 (10), p.4722-4731
Main Authors: Antwi, Kwasi, Hostetter, Galen, Demeure, Michael J, Katchman, Benjamin A, Decker, G. Anton, Ruiz, Yvette, Sielaff, Timothy D, Koep, Lawrence J, Lake, Douglas F
Format: Article
Language:English
Subjects:
Adolescent
Adult
Blotting, Western
Carcinoma, Ductal - metabolism
Chromatography, Liquid
Female
Humans
Immunohistochemistry
Male
Middle Aged
Oxidoreductases Acting on Sulfur Group Donors
Pancreatic Neoplasms - metabolism
Peptides - blood
Peptides - metabolism
Protein Stability
Proteome - analysis
Tandem Mass Spectrometry
Thioredoxins - blood
Thioredoxins - metabolism
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Summary:Blood circulates through nearly every organ including tumors. Therefore, plasma is a logical source to search for tumor-derived proteins and peptides. The challenge with plasma is that it is a complex bodily fluid composed of high concentrations of normal host proteins that obscure identification of tumor-derived molecules. To simplify plasma, we examined a low molecular weight (LMW) fraction (plasma peptidome) using liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. In the plasma peptidome of patients with ductal adenocarcinoma of the pancreas (DAP), a prominent peptide was identified from the QSOX1 parent protein. This peptide is stable in whole blood over 24 h and was present in 16 of 23 DAP patients and 4 of 5 patients with intraductal papillary mucinous neoplasm (IPMN). QSOX1 peptides were never identified in the plasma peptidome from 42 normal healthy donors using the same methods. Immunohistochemical staining of DAP tissue sections with anti-QSOX1 antibody shows overexpression of QSOX1 in tumor but not in adjacent stroma or normal ducts. Three of four pancreas tumor cell lines also express QSOX1 protein by Western blot analysis. This is the first report of QSOX1 peptides in plasma from DAP patients and makes the rare connection between a peptide in plasma from cancer patients and overexpression of the parent protein in tumors.
ISSN:1535-3893
1535-3907
DOI:10.1021/pr900414f