a1-3/4 fucosylation at Asn 241 of ß-haptoglobin is a novel marker for colon cancer: A combinatorial approach for development of glycan biomarkers

被引：52

作者：

Park, Seung-Yeol ^{[1
]}

Lee, Sung-Hyeon ^{[1
]}

Kawasaki, Nana ^{[2
]}

Itoh, Satsuki ^{[2
]}

Kang, Keunsoo ^{[1
]}

Ryu, Soo Hee ^{[1
]}

Hashii, Noritaka ^{[2
]}

Kim, Jin-Man ^{[3
,4
,5
]}

Kim, Ji-Yeon ^{[6
]}

Kim, Jung Hoe ^{[1
]}

机构：

[1] Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea

[2] Natl Inst Hlth Sci, Div Biol Chem & Biol, Tokyo 1588501, Japan

[3] Chungnam Natl Univ, Sch Med, Dept Pathol, Taejon, South Korea

[4] Chungnam Natl Univ, Sch Med, Canc Res Inst, Taejon, South Korea

[5] Chungnam Natl Univ, Sch Med, Infect Signaling Network Res Ctr, Dept Pathol, Taejon, South Korea

[6] Chungnam Natl Univ, Sch Med, Dept Surg, Taejon 301131, South Korea

来源：

INTERNATIONAL JOURNAL OF CANCER | 2012年 / 130卷 / 10期

基金：

新加坡国家研究基金会;

关键词：

haptoglobin; colon cancer; lectin blotting; microarray; mass spectrometry; PANCREATIC-CANCER; HEPATOCELLULAR-CARCINOMA; GLYCOSYLATION ANALYSIS; SERUM GLYCOPROTEINS; N-GLYCOSYLATION; CELL-LINES; EXPRESSION; ADENOCARCINOMA; CORRELATE; PROTEINS;

D O I：

10.1002/ijc.26288

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Aberrant glycosylation has been observed in many types of cancer, but the mechanism of glycosylation change is still poorly understood. To elucidate relationships between glycosylation and colon cancer progression, we analyzed glycosylation status of beta-haptoglobin (beta-Hp) obtained from 46 cancer patients, 14 inflammatory bowel disease patients and 38 normal subjects. Aleuria aurantia lectin reactivity with cancer beta-Hp was much higher than in the other two study groups. These results were confirmed by lectin blotting and microarray assay using other lectins directed to fucosyl residues. Levels of such glycans were correlated with stage of colon cancer progression. Reactivity with fucosylated glycans was eliminated by treatment with a1-3/4 fucosidase but not a1-6 fucosidase, indicating that enhanced lectin reactivity with the fucose moiety of colon cancer beta-Hp is due to Fuca1-3/4GlcNAc. Moreover, site-specific glycan occupancy was determined by sequential LC/MS analysis. Mass spectrometric analysis showed that fucosylation of beta-Hp was higher in colon cancer patients than in other subjects. In particular, fucosylation at Asn 241 of beta-Hp in sera of colon cancer patients was clearly higher than in the other groups, and the ratio of fucosylated glycopeptides containing Asn 241 decreased greatly after treatment with a1-3/4 fucosidase. In conclusion, the level of a1-3/4 fucosyl epitope at Asn 241 of beta-Hp is potentially useful as a novel marker for colon cancer.

引用

页码：2366 / 2376

页数：11

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