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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

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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.

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Abbreviations

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

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Authors and Affiliations

  1. Graduate School of Advanced Sciences of Matter, Hiroshima University, 1-3-1 Kagamiyama, Higashi-hiroshima, 739-8530, Japan

    Shiro Takahashi, Taiki Sugiyama & Miyako Nakano

  2. Department of Molecular Biochemistry & Clinical Investigation, Osaka University Graduate School of Medicine, Osaka, Japan

    Mayuka Shimomura, Yoshihiro Kamada & Eiji Miyoshi

  3. Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan

    Kazutoshi Fujita & Norio Nonomura

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  1. Shiro Takahashi
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  2. Taiki Sugiyama
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  3. Mayuka Shimomura
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  4. Yoshihiro Kamada
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  5. Kazutoshi Fujita
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  7. Eiji Miyoshi
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  8. Miyako Nakano
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Correspondence to Miyako Nakano.

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Takahashi, S., Sugiyama, T., Shimomura, M. et al. 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. Glycoconj J 33, 471–482 (2016). https://doi.org/10.1007/s10719-016-9653-7

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