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: possible implication for the differential diagnosis of cancer

Takahashi Shiro

Sugiyama Taiki

Shimomura Mayuka

Kamada Yoshihiro

Fujita Kazutoshi

Nonomura Norio

Miyoshi Eiji

Nakano Miyako

Glycoconjugate Journal

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 observed 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 in only 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.

fucosylated haptoglobin

gastroenterological cancer

metastatic prostate cancer

linkage of fucose

site-specific analysis

eng

Springer Verlag

© Springer Science+Business Media New York 2016

This is a post-peer-review, pre-copyedit version of an article published in Glycoconjugate Journal. The final authenticated version is available online at: https://doi.org/10.1007/s10719-016-9653-7

This is not the published version. Please cite only the published version. この論文は出版社版ではありません。引用の際には出版社版をご確認、ご利用ください。

[ISSN] 0282-0080

[ISSN] 1573-4986

[DOI] 10.1007/s10719-016-9653-7

[PMID] 26869352

[DOI] https://doi.org/10.1007/s10719-016-9653-7