Pancreatic cancer places a significant burden on society and has no effective early detection method. A glyco-microarray approach will be used to search for early detection biomarkers of pancreatic cancers in human plasma. We will use multi-dimensional liquid phase fractionation of intact N-linked plasma glycoproteins previously isolated by lectin affinity columns. The multi-dimensional fractionation will involve nonporous chromatography to separate the glycoproteins and liquid capillary isoelectric focusing to separate protein isoforms, thus providing a means to collect isolated glycoforms in liquid phase for further analysis. UV absorption detection will allow profiling of changes between cancer versus control. Proteins of interest will be identified by mass spectrometry. These fractions will be spotted on nitrocellulose-coated microscope slides to produce a natural glycoprotein microarray, and will be interrogated by various fluorescently-labeled lectins to probe each microarray spot for the presence of different glycan moieties. Patients with pancreatic adenocarcinoma, pancreatic mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMNs), chronic pancreatitis. Type II diabetes for 10 or more year, and normals patients will serve as the disease categories of interest. Plasma from 30 participants per category will be analyzed to search for patterns that can discriminate patients with MCNs/IPMNS from the other disease categories. Glycoproteins that reveal such changes will be analyzed by QIT-TOF (MALDI-MSn) mass spectrometry to examine the detailed changes in glycan structure that may serve as biomarkers. Once the potential bio-markers are identified, high throughput antibody arrays will be used to establish information necessary to plan a validation study. This will include initial analytical validation to define the within and between indi-vidual varaibility using 30 participants per disease cateogry. Next, preliminary decision analysis will be per-fonned on an open label set of assays from 50 participants per disease category. Finally, a blinded set of assays will be done on 95 particiants per disease category. This systematic approach to examing the analytic characteristics of the assay will provide information requhed to plan a valdiation of these early detection biomarkers for pancreatic cancer. It is envisioned that these biomarkers could be used for early detection among high risk groups such a smoker, patients with long term Type II diabetes or chronic pancreatitis.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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University of Michigan Ann Arbor
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Triner, Daniel; Xue, Xiang; Schwartz, Andrew J et al. (2017) Epithelial Hypoxia-Inducible Factor 2? Facilitates the Progression of Colon Tumors through Recruiting Neutrophils. Mol Cell Biol 37:
An, Mingrui; Lohse, Ines; Tan, Zhijing et al. (2017) Quantitative Proteomic Analysis of Serum Exosomes from Patients with Locally Advanced Pancreatic Cancer Undergoing Chemoradiotherapy. J Proteome Res 16:1763-1772
Djuric, Zora; Aslam, Muhammad Nadeem; Simon, Becky R et al. (2017) Effects of fish oil supplementation on prostaglandins in normal and tumor colon tissue: modulation by the lipogenic phenotype of colon tumors. J Nutr Biochem 46:90-99
Dosch, Joseph; Ziemke, Elizabeth; Wan, Shanshan et al. (2017) Targeting ADAM17 inhibits human colorectal adenocarcinoma progression and tumor-initiating cell frequency. Oncotarget 8:65090-65099
Ulintz, Peter J; Greenson, Joel K; Wu, Rong et al. (2017) Lymph Node Metastases in Colon Cancer are Polyclonal. Clin Cancer Res :
Stoffel, Elena M; Koeppe, Erika; Everett, Jessica et al. (2017) Germline Genetic Features of Young Individuals with Colorectal Cancer. Gastroenterology :
Djuric, Zora (2017) Obesity-associated cancer risk: the role of intestinal microbiota in the etiology of the host proinflammatory state. Transl Res 179:155-167
Parsels, Leslie A; Karnak, David; Parsels, Joshua D et al. (2017) PARP1 Trapping and DNA Replication Stress Enhance Radiosensitization with Combined WEE1 and PARP Inhibitors. Mol Cancer Res :
Demitrack, Elise S; Samuelson, Linda C (2017) Notch as a Driver of Gastric Epithelial Cell Proliferation. Cell Mol Gastroenterol Hepatol 3:323-330
Djuric, Zora; Aslam, Muhammad Nadeem; Simon, Becky R et al. (2017) Fatty acid and lipidomic data in normal and tumor colon tissues of rats fed diets with and without fish oil. Data Brief 13:661-666

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