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Glycoconjugate Journal

, Volume 33, Issue 3, pp 471–482 | Cite as

Site-specific and linkage analyses of fucosylated N-glycans on haptoglobin in sera of patients with various types of cancer: possible implication for the differential diagnosis of cancer

  • Shiro Takahashi
  • Taiki Sugiyama
  • Mayuka Shimomura
  • Yoshihiro Kamada
  • Kazutoshi Fujita
  • Norio Nonomura
  • Eiji Miyoshi
  • Miyako Nakano
Original Article

Abstract

Fucosylation is an important type of glycosylation involved in cancer, and fucosylated proteins could be employed as cancer biomarkers. Previously, we reported that fucosylated N-glycans on haptoglobin in the sera of patients with pancreatic cancer were increased by lectin-ELISA and mass spectrometry analyses. However, an increase in fucosylated haptoglobin has been reported in various types of cancer. To ascertain if characteristic fucosylation is observed in each cancer type, we undertook site-specific analyses of N-glycans on haptoglobin in the sera of patients with five types of operable gastroenterological cancer (esophageal, gastric, colon, gallbladder, pancreatic), a non-gastroenterological cancer (prostate cancer) and normal controls using ODS column LC-ESI MS. Haptoglobin has four potential glycosylation sites (Asn184, Asn207, Asn211, Asn241). In all cancer samples, monofucosylated N-glycans were significantly increased at all glycosylation sites. Moreover, difucosylated N-glycans were detected at Asn 184, Asn207 and Asn241 only in cancer samples. Remarkable differences in N-glycan structure among cancer types were not observed. We next analyzed N-glycan alditols released from haptoglobin using graphitized carbon column LC-ESI MS to identify the linkage of fucosylation. Lewis-type and core-type fucosylated N-glycans were increased in gastroenterological cancer samples, but only core-type fucosylated N-glycan was relatively increased in prostate cancer samples. In metastatic prostate cancer, Lewis-type fucosylated N-glycan was also increased. These data suggest that the original tissue/cell producing fucosylated haptoglobin is different in each cancer type and linkage of fucosylation might be a clue of primary lesion, thereby enabling a differential diagnosis between gastroenterological cancers and non-gastroenterological cancers.

Keywords

Fucosylated haptoglobin Gastroenterological cancer Metastatic prostate cancer Linkage of fucose Site-specific analysis 

Abbreviation

LC-ESI MS

Liquid chromatography-electrospray ionization-mass spectrometry

Hpt

Haptoglobin

NV

Normal volunteers

Eso

Esophageal cancer

Gas

Gastric cancer

Col

Colon cancer

Pan

Pancreatic cancer

Gal

Gallbladder cancer

Pro

Prostate cancer

Supplementary material

10719_2016_9653_MOESM1_ESM.pdf (336 kb)
ESM 1 (PDF 335 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Shiro Takahashi
    • 1
  • Taiki Sugiyama
    • 1
  • Mayuka Shimomura
    • 2
  • Yoshihiro Kamada
    • 2
  • Kazutoshi Fujita
    • 3
  • Norio Nonomura
    • 3
  • Eiji Miyoshi
    • 2
  • Miyako Nakano
    • 1
  1. 1.Graduate School of Advanced Sciences of MatterHiroshima UniversityHigashi-hiroshimaJapan
  2. 2.Department of Molecular Biochemistry & Clinical InvestigationOsaka University Graduate School of MedicineOsakaJapan
  3. 3.Department of UrologyOsaka University Graduate School of MedicineOsakaJapan

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