Pancreatic cancer is now the fourth leading cause of
cancer deaths in the United States, and it is associated with an alarmingly low 5-year survival rate of 5%. However, a patient's prognosis is considerably improved when the malignant lesions are identified at an early stage of the disease and removed by surgical resection. Unfortunately, the absence of a practical screening strategy and clinical diagnostic test for identifying premalignant lesions within the pancreas often prevents early detection of
pancreatic cancer. To aid in the development of a molecular screening system for early detection of the disease, we have performed glycomic and glycoproteomic profiling experiments on 21
pancreatic cyst fluid samples, including fluids from mucinous
cystic neoplasms and intraductal papillary
mucinous neoplasms, two types of mucinous
cysts that are considered high risk to undergo malignant transformation. A total of 80
asparagine-linked (N-linked)
glycans, including high
mannose and complex structures, were identified. Of special interest was a series of complex N-linked
glycans containing two to six
fucose residues, located predominantly as substituents on β-
lactosamine extensions. Following the observation of these "hyperfucosylated"
glycans, bottom-up proteomics experiments utilizing a label-free quantitative approach were applied to the investigation of two sets of tryptically digested
proteins derived from the cyst fluids: 1) all soluble
proteins in the raw samples and 2) a subproteome of the soluble cyst fluid
proteins that were selectively enriched for fucosylation through the use of surface-immobilized
Aleuria aurantia lectin. A comparative analysis of these two proteomic data sets identified
glycoproteins that were significantly enriched by
lectin affinity. Several candidate
glycoproteins that appear hyperfucosylated were identified, including
triacylglycerol lipase and pancreatic α-
amylase, which were 20- and 22-fold more abundant, respectively, following A. aurantia
lectin enrichment.