Chronic pancreatitis, a destructive disease of the pancreas, is difficult to diagnosis and can present with a variety of symptoms. The incidence of chronic pancreatitis is not known;hospital admission and discharge summaries suggest at least 60,000 patients in the US per year, however these are under-estimates and it is clear that many patients have occult disease. The financial burden of pancreatitis to society is substantial: with loss of work and health care costs, the burden approaches $2.5 billion annually. There are currently no good bloods tests for the diagnosis of chronic pancreatitis;endoscopic studies and CT scan are the standard approaches for the diagnosis, with endoscopic ultrasound (EUS) combined with pancreatic function tests (PFT) being the most sensitive. We propose a carefully constructed algorithm for the development of biomarkers for chronic pancreatitis. Our technology for candidate biomarkers discovery uses state-of-the- art proteomics. Our group has an excellent experience working together and each member is considered an expert in their applied field. The preliminary data reveals that we can detect the proteins that underlie pancreatitis and we provide proof of principle that the proteins discovered in tissue are measurable in the blood by ELISA. The feasibility of the proposal is further supported by the fact that we have recruited more than one third of the patients required for the study, we demonstrate that the ITRAQ proteomics techniques are robust and accurate, and that there appears to be no problem with heterogeneity in the pancreatitis proteome based on differences in the gender or ethnic origin of the patient. Our preliminary results support our thesis of protein discovery leading to a measurable biomarker for pancreatitis and also demonstrate the ability of the team to work effectively and successfully. The cohort in which the biomarkers will be developed are highly defined and represent the clinical setting in which the biomarker would be used. The initial biomarker studies look promising. An accurate biomarker for chronic pancreatitis would be of enormous clinical benefit and could save time and costs in comparison to the current gold standard of endoscopic testing for the disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK081368-02
Application #
7936364
Study Section
Kidney, Nutrition, Obesity and Diabetes (KNOD)
Program Officer
Serrano, Jose
Project Start
2009-09-30
Project End
2012-08-31
Budget Start
2010-09-01
Budget End
2012-08-31
Support Year
2
Fiscal Year
2010
Total Cost
$753,143
Indirect Cost
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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Chen, Ru; Pan, Sheng; Ottenhof, Niki A et al. (2012) Stromal galectin-1 expression is associated with long-term survival in resectable pancreatic ductal adenocarcinoma. Cancer Biol Ther 13:899-907
Pan, Sheng; Chen, Ru; Brand, Randall E et al. (2012) Multiplex targeted proteomic assay for biomarker detection in plasma: a pancreatic cancer biomarker case study. J Proteome Res 11:1937-48
Pan, Sheng; Chen, Ru; Stevens, Tyler et al. (2011) Proteomics portrait of archival lesions of chronic pancreatitis. PLoS One 6:e27574
Pan, Sheng; Chen, Ru; Aebersold, Ruedi et al. (2011) Mass spectrometry based glycoproteomics--from a proteomics perspective. Mol Cell Proteomics 10:R110.003251
Pan, Sheng; Chen, Ru; Crispin, David A et al. (2011) Protein alterations associated with pancreatic cancer and chronic pancreatitis found in human plasma using global quantitative proteomics profiling. J Proteome Res 10:2359-76
Chen, Ru; Pan, Sheng; Duan, Xiaobo et al. (2010) Elevated level of anterior gradient-2 in pancreatic juice from patients with pre-malignant pancreatic neoplasia. Mol Cancer 9:149