N-glycosylation status of β-haptoglobin in sera of patients with prostate cancer vs. benign prostate diseases
N-glycosylation status of β-haptoglobin in sera of patients with prostate cancer vs. benign prostate diseases
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DOI：
10.3892/ijo_00000490
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发表时间：
2010-01-01
影响因子：
5.2
通讯作者：
Hakomori, Sen-Itiroh
中科院分区：
文献类型：
--
作者：
Yoon, Seon-Joo;Park, Seung-Yeol;Hakomori, Sen-Itiroh
研究了从前列腺癌患者血清中分离的纯化的β-触珠蛋白的N-糖基化状态，并与来自良性前列腺疾病患者或正常受试者的血清进行比较。如下所述，进行了两种不同的方法，一种基于凝集素和抗体与β-触珠蛋白的油结合，另一种基于从β-触珠蛋白释放的N-连接聚糖的质谱分析。部分结果可用于前列腺癌与前列腺良性疾病的鉴别诊断。i）对于前列腺癌和高级别前列腺上皮内瘤形成的病例，菜豆凝集素（PHA-L）（定义存在于三触角或四触角N-连接聚糖中的GlcNAc β 6 Man α 6 Man侧链）与β-触珠蛋白的结合高于良性疾病。一些癌症病例中，确定Fuc α 3-、α 4-或α 6-GlcNAc的橙黄粉虱凝集素（AAL）或针对唾液酸-Le（x）的单克隆抗体与β-触珠蛋白的结合也高于良性疾病。许多其他凝集素和抗体显示不与β-触珠蛋白结合，或者在癌症与良性疾病之间没有显着差异。ii）肽N-糖苷酶-F释放的β-触珠蛋白的N-连接聚糖的质谱分析显示前列腺癌病例中单唾液酸三触角结构的表达增强。因此，PHA-L与来自患者血清的亲和纯化的β-触珠蛋白的结合可以导致用于前列腺癌与良性前列腺疾病的鉴别诊断的有用工具的开发。
N-glycosylation status of purified beta-haptoglobin separated from sera of patients with prostate cancer was studied in comparison to that of sera from patients with benign prostate diseases, or normal subjects. Two different approaches, as summarized below, one based oil binding of lectins and antibodies to beta-haptoglobin, the other on mass spectrometry of released N-linked glycans from beta-haptoglobin, were performed. Some of the results were useful for distinction of prostate cancer vs. benign prostate diseases. i) Binding of Phaseolus vidgaris-L lectin (PHA-L), defining the GlcNAc beta 6Man alpha 6Man side chain present in tri- or tetra-antennary N-linked glycans, to beta-haptoglobin was higher for cases of prostate cancer and high-grade prostate intraepithelial neoplasia than for benign diseases. Binding of Aleuria aurantia lectin (AAL) defining Fuc alpha 3-, alpha 4-, or alpha 6-GlcNAc, or mono-clonal antibody directed to sialyl-Le(x), to beta-haptoglobin was also higher for some of the cancer cases than for benign diseases. Many other lectins and antibodies showed no binding to beta-haptoglobin, or showed no significant difference between cancer vs. benign diseases. ii) Mass spectrometric analysis of N-linked glycans of beta-haptoglobin released by Peptide N-glycosidase-F showed enhanced expression of monosialyl tri-antennary structures in prostate cancer cases. Thus, binding of PHA-L to affinity-purified beta-haptoglobin from sera of patients could lead to development of useful tools for differential diagnosis of prostate cancer vs. benign prostate diseases.