Ph.D. Thesis Defense

Christina Wilson, MS

Graduate Student in Analytical Toxicology

“Comparative Glycoproteomics Analysis In Cancer”

Tuesday, November 14, 2006

10:00 a.m.

ADDL 143

ABSTRACT:

Increased fucosylation of cell surface glycoproteins has been correlated with malignancy and metastatic potential. Because tumor-associated fucosylated proteins are often liberated from the cell surface and can be detected in the blood stream, pathological changes in the blood or tissues are likely to be reflected in serum proteins. Recent advances in proteomics technologies have made it possible to analyze for panels of serum proteins, providing a means screen for multiple protein biomarkers relevant to disease. Using a serum-based glycoproteomics method, changes in fucosylated serum peptides from dogs with lymphoma and transitional cell carcinoma (TCC) of the urinary bladder have been evaluated. From the peptide pattern profiles generated in one dog with lymphoma, pre-chemotherapy (lymphoma), post-chemotherapy (remission), and relapse (recurrence of lymphoma) serum samples were analyzed and compared. The results from this study revealed that the majority of the fucosylated peptides that increased with lymphoma (pre-chemotherapy) decreased following chemotherapy when the dog was in clinical remission, and subsequently increased during relapse of the cancer. When the pre-chemotherapy serum of this and two other dogs with lymphoma were analyzed and compared to normal serum, nearly all of the peptides identified in the three dogs increased with lymphoma. In the TCC study, serum from two dogs were analyzed and compared. When the sera from these two dogs were compared to normal serum, greater than 70% of the peptides that changed increased with TCC. When comparing all of the peptides that increased in the dogs with lymphoma with those that increased in the dogs with TCC, only 2 peptides were similar in all five dogs. This indicates that some of the changes in the fucosylated peptides observed to be unique to lymphoma or TCC are from proteins specific for either lymphoma or TCC of the urinary bladder. These results emphasize the potential of glycoproteomics for use in the diagnosis of cancer, monitoring patient response to chemotherapy, and indicating recurrence of the disease.