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
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
复制标题
DOI：
10.1002/ijc.26288
复制
发表时间：
2012-05-15
影响因子：
6.4
通讯作者：
Kim, Jung Hoe
中科院分区：
文献类型：
--
作者：
Park, Seung-Yeol;Lee, Sung-Hyeon;Kim, Jung Hoe
在许多类型的癌症中都观察到了异常的糖基化，但糖基化变化的机制仍然知之甚少。为了阐明糖基化与结肠癌进展之间的关系，我们分析了从 46 名癌症患者、14 名炎症性肠病患者和 38 名正常受试者中获得的 β-触珠蛋白 (beta-Hp) 的糖基化状态。 Aleuria aurantia 凝集素与癌症 β-Hp 的反应性远高于其他两个研究组。这些结果通过使用针对岩藻糖基残基的其他凝集素的凝集素印迹和微阵列测定得到证实。这些聚糖的水平与结肠癌进展阶段相关。通过使用α1-3/4岩藻糖苷酶而非α1-6岩藻糖苷酶处理，可以消除与岩藻糖基化聚糖的反应性，这表明凝集素与结肠癌β-Hp的岩藻糖部分的反应性增强是由于Fuca1-3/4GlcNAc。此外，通过连续 LC/MS 分析确定位点特异性聚糖占据。质谱分析表明，结肠癌患者的 β-Hp 岩藻糖基化程度高于其他受试者。特别是结肠癌患者血清中β-Hp第241位岩藻糖基化明显高于其他组，且经α1-3/4岩藻糖苷酶处理后，含有第241位Asn的岩藻糖基化糖肽比例大幅下降。总之，β-Hp Asn 241 处的 a1-3/4 岩藻糖基表位水平可能可用作结肠癌的新型标记物。
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.