Rather than looking for specific cancer biomarkers (proteins or glycosylated proteins), we emphasize quantitative deglycosylation (removal of glycans) in unfractionated biological samples and displaying the removed glycans in quantitative glycan maps. Comparing glycomic profiles originating from healthy and diseased individuals should allow the assignment of structural changes associated with cancer. On the other hand, prognosis or a differential assessment of patients'health then relies on the isotopically-aided quantitative MS measurements of such glycan patterns. In the first two phases of our proposed research, clinically relevant samples will be screened through our well-established procedures while using the state-of- the-art MS-based methodologies and capillary electrophoresis. In Phase 1, the glycomic patterns of human blood serum collected from healthy females and males will be compared to those collected from ovarian, prostate, lung and colon cancer patients. Through bioinformatic and statistical evaluation a list of glycan markers that are associated with each type of cancer or with all types of cancer to be studied will be determined. This is necessary to establish quantitative trends in glycosylation or the occurrence of """"""""glycosylation aberrations"""""""" and link these measurements to positively identified glycan structures. Glycomic profiles acquired for the same samples by CE-LIF will aid in determining changes that are due to changes in structural isomers which cannot be determined through MS. In Phase 2, the glycomic maps of human blood serum of cancer before and after treatment with a specific drug will be compared. In this phase, changes in the set of glycans defined in Phase 1 will be closely monitored and their changes as a result of cancer progression or remission will be evaluated. Phase 2 results will confirm or refute the potential glycan structures that will be defined as potential biomarkers in Phase 1. Upon the identification of these specific glycan changes or the set of glycan structures that change as a result of disease progression or remission, the potential of a faster screening approach such as lectin or antibody microarrays will be investigated. This is the aim of Phase 3 of this study which will focus on defining the best analytical tools that could be utilized as diagnostic and prognostic tool.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA128535-05
Application #
8104031
Study Section
Special Emphasis Panel (ZCA1-SRRB-4 (J1))
Program Officer
Wagner, Paul D
Project Start
2007-08-08
Project End
2012-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
5
Fiscal Year
2011
Total Cost
$361,949
Indirect Cost
Name
Indiana University Bloomington
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
006046700
City
Bloomington
State
IN
Country
United States
Zip Code
47401
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Mann, Benjamin F; Goetz, John A; House, Michael G et al. (2012) Glycomic and proteomic profiling of pancreatic cyst fluids identifies hyperfucosylated lactosamines on the N-linked glycans of overexpressed glycoproteins. Mol Cell Proteomics 11:M111.015792

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