Our previous studies found that the concentration of fucosylated haptoglobin had increased in the sera of patients with pancreatic cancer compared with those of other types of cancer and normal controls. Haptoglobin, an acute phase protein, has four potential N-glycosylation sites, although it remains unknown which site is responsible for the change in fucosylated N-glycans. In this study, site-specific N-glycan structures of haptoglobin in serum obtained from patients with pancreatic cancer or chronic pancreatitis were analyzed using liquid chromatography-electrospray ionization mass spectrometry. Mass spectrometry analyses demonstrated that concentrations of total fucosylated, di-, tri- and tetra-branched glycans of haptoglobin were increased in the sera of pancreatic cancer patients. Tri-antennary N-glycans containing a Lewis X-type Fuc were markedly increased at the Asn211 site of haptoglobin N-glycans. This approach could make a differential diagnosis for tumor-forming pancreatitis form pancreatic cancer in one complicated case. Furthermore, we recently identified a factor to stimulate the production of fucosylated haptoglobin in the conditioned medium of a pancreatic cancer cell line. Thus, the present study provides evidence that site-specific analyses of fucosylated N-glycans may be useful as a novel tumor marker for pancreatic cancer.
