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 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.
Antwi
Kwasi
K
School of Life Sciences, Arizona State University, Tempe, Arizona 85287-4501, USA.
Hostetter
Galen
G
Demeure
Michael J
MJ
Katchman
Benjamin A
BA
Decker
G Anton
GA
Ruiz
Yvette
Y
Sielaff
Timothy D
TD
Koep
Lawrence J
LJ
Lake
Douglas F
DF
D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D044584:Carcinoma, Ductal / Q000378:metabolism*; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D050862:Oxidoreductases Acting on Sulfur Group Donors; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010455:Peptides / Q000097:blood* / Q000378:metabolism; D055550:Protein Stability; D020543:Proteome / Q000032:analysis*; D053719:Tandem Mass Spectrometry; D013879:Thioredoxins / Q000097:blood* / Q000378:metabolism
D010455:Peptides; D020543:Proteome; D013879:Thioredoxins; D050862:Oxidoreductases Acting on Sulfur Group Donors; C117183:QSOX1 protein, human