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

被引:51
作者
Antwi, Kwasi [1 ]
Hostetter, Galen [2 ]
Demeure, Michael J. [2 ]
Katchman, Benjamin A. [1 ]
Decker, G. Anton [3 ]
Ruiz, Yvette [1 ]
Sielaff, Timothy D. [4 ]
Koep, Lawrence J. [5 ]
Lake, Douglas F. [1 ]
机构
[1] Arizona State Univ, Sch Life Sci, Tempe, AZ 85287 USA
[2] Translat Genom Res Inst, Phoenix, AZ 85004 USA
[3] Mayo Clin Scottsdale, Scottsdale, AZ 85259 USA
[4] Virginia Piper Canc Inst, Minneapolis, MN 55407 USA
[5] Banner Good Samaritan Med Ctr, Phoenix, AZ 85006 USA
关键词
Liquid chromatography; tandem mass spectrometry; collision-activated dissociation; plasma; peptidome; pancreatic cancer; immunohistochemistry; Western blot; PAPILLARY MUCINOUS NEOPLASMS; TANDEM MASS-SPECTROMETRY; HUMAN SERUM PROTEOME; BIOMARKER DISCOVERY; INTRAEPITHELIAL NEOPLASIA; SULFHYDRYL OXIDASES; IDENTIFICATION; ANTIGEN; ADENOCARCINOMA; INVOLVEMENT;
D O I
10.1021/pr900414f
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:4722 / 4731
页数:10
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