Pancreatic cancer is a highly lethal disease that is very difficult to diagnose. The high mortality of this disease is predominantly due to the advanced stage of disease at the time of diagnosis and a lack of effective treatments. Due to the low prevalence of pancreatic cancer (0.01%), early detection would be most cost-effective in screening increased-risk populations, such as new-onset type-2 diabetics. Clinical and research studies have substantiated the link between pancreatic cancer and new-onset type-2 diabetes. Development of a highly accurate blood-based test to detect pancreatic cancer in this population would represent a breakthrough in early detection of pancreatic cancer. Such a blood test, if used on an annual basis in this higher-risk population, could serve as an effective and inexpensive method for initial targeted screening. In this project, we proposed to develop and characterize a blood-based proteomics signature that allows early detection of pancreatic cancer patients with new-onset diabetics.
The Specific Aims are as follows:
Specific Aim 1 : unbiased global discovery of differential proteins associated with pancreatic cancer in the blood of diabetic patients using quantitative proteomics;
Specific Aim 2 : development of targeted proteomics assay for 35 selected biomarker candidates;
Specific Aim 3 : establishment of a proteomics signature (biomarker panel) for detecting early stage pancreatic cancer in diabetic patients;
Specific Aim 4 : evaluation of the proteomics signature in detecting pancreatic cancer in asymptomatic patients. This proposal builds on our decade-long systematic study of pancreatic tumorigenesis, the rich resource of previous discoveries in pancreatic cancer biomarker development, well-characterized study cohorts from different institutions, as well as cutting-edge proteomics platform technologies that we have developed and implemented. Successful development of a blood-based assay to facilitate the early detection of pancreatic cancer for diabetic patients would alleviate the current prolonged work-up of higher-risk populations and provide critically important interception opportunities to treat earlier stage cancer.

Public Health Relevance

We propose to apply cutting-edge targeted proteomics technologies to develop a blood-based test for early detection of pancreatic cancer in diabetic patients. Successful development of such a blood test, if used on an annual basis in this higher-risk population, could serve as an effective method for initial targeted screening, providing critically important intervention opportunities to treat earlier stage cancer.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Cancer Biomarkers Study Section (CBSS)
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Rinaudo, Jo Ann S
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University of Washington
Internal Medicine/Medicine
Schools of Medicine
United States
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Nigjeh, Eslam N; Chen, Ru; Allen-Tamura, Yasuko et al. (2017) Spectral library-based glycopeptide analysis-detection of circulating galectin-3 binding protein in pancreatic cancer. Proteomics Clin Appl 11:
Chen, Ru; Lai, Lisa A; Sullivan, Yumi et al. (2017) Disrupting glutamine metabolic pathways to sensitize gemcitabine-resistant pancreatic cancer. Sci Rep 7:7950
Nigjeh, Eslam N; Chen, Ru; Brand, Randall E et al. (2017) Quantitative Proteomics Based on Optimized Data-Independent Acquisition in Plasma Analysis. J Proteome Res 16:665-676
Pan, Sheng; Brentnall, Teresa A; Chen, Ru (2016) Glycoproteins and glycoproteomics in pancreatic cancer. World J Gastroenterol 22:9288-9299
Pan, Sheng; Brentnall, Teresa A; Chen, Ru (2015) Proteomics analysis of bodily fluids in pancreatic cancer. Proteomics 15:2705-15
Chen, Ru; Dawson, David W; Pan, Sheng et al. (2015) Proteins associated with pancreatic cancer survival in patients with resectable pancreatic ductal adenocarcinoma. Lab Invest 95:43-55