Site‐specific analysis of N‐glycans on haptoglobin in sera of patients with pancreatic cancer: A novel approach for the development of tumor markers

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Abstract
It was found in our previous studies that the concentration of fucosylated haptoglobin had increased in the sera of patients with pancreatic cancer (PC) compared to 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 the present study, site‐specific N‐glycan structures of haptoglobin in sera obtained from patients with PC or chronic pancreatitis (CP) 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 increased in the sera of PC patients. Tri‐antennary N‐glycans containing a Lewis X‐type fucose markedly increased at the Asn211 site of haptoglobin N‐glycans. While fucosylated N‐glycans derived from serum haptoglobin of patients with CP slightly increased, di‐fucosylated tetra‐antennary N‐glycans were observed only at this site in PC patients, and were absent in the haptoglobin of normal controls and individuals with CP. Thus, the present study provides evidence that site‐specific analyses of N‐glycans may be useful as novel tumor markers for PC.