Tajiri Michiko, Ohyama Chikara, Wada Yoshinao
Department of Molecular Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo-cho Izumi, Osaka 594-1101, Japan.
Glycobiology. 2008 Jan;18(1):2-8. doi: 10.1093/glycob/cwm117. Epub 2007 Oct 23.
The oligosaccharide structures of prostate specific antigen (PSA) are expected to be useful in discriminating prostate cancer from benign conditions both accompanied by increased serum PSA levels. A large proportion of PSA forms a covalent complex with a glycoprotein, alpha(1)-antichymotrypsin, in human blood. In the present study, the glycan profiles of free and complexed forms of PSA from cancer patient serum and of seminal plasma PSA were compared by analyzing the glycopeptides obtained by lysylendopeptidase digestion of the electrophoretically separated PSA with mass spectrometry. The profiles of the PSA N-glycans from the free and complexed molecules were quite similar to each other and consisted of fucosylated biantennary oligosaccharides as the major class. They were mostly sialylated, and a considerable sialic acid fraction was alpha2,3-linked as determined by Streptococcus pneumoniae neuraminidase digestion of the glycopeptides. In the seminal plasma PSA, high-mannose and hybrid types of oligosaccharides were predominant, and the sialic acids attached to the latter as well as to biantennary oligosaccahrides were exclusively alpha2,6-linked because they were removed by Arthrobacter ureafaciens neuraminidase but resistant to S. pneumoniae neuraminidase. Complex-type oligosaccharides from other sources were found in the seminal plasma sample, indicating that analysis of released glycans carries a risk of being misleading. The results suggest that identification of alpha2,3-linked sialic acids on PSA potentially discriminates malignant from benign conditions, if the analysis is applied to oligosaccharides specifically attached to the N-glycosylation site of PSA in either a free or a complexed form in the serum.
前列腺特异性抗原（PSA）的寡糖结构有望用于鉴别前列腺癌与血清PSA水平均升高的良性疾病。在人体血液中，很大一部分PSA与一种糖蛋白α(1)-抗胰凝乳蛋白酶形成共价复合物。在本研究中，通过对经电泳分离的PSA用赖氨酰内肽酶消化后获得的糖肽进行质谱分析，比较了癌症患者血清中游离和复合形式的PSA以及精浆PSA的聚糖谱。游离和复合分子的PSA N-聚糖谱彼此非常相似，主要由岩藻糖基化的双天线寡糖组成。它们大多被唾液酸化，通过糖肽的肺炎链球菌神经氨酸酶消化确定，相当一部分唾液酸以α2,3连接。在精浆PSA中，高甘露糖型和杂合型寡糖占主导，连接到后者以及双天线寡糖上的唾液酸均仅为α2,6连接，因为它们可被解脲节杆菌神经氨酸酶去除，但对肺炎链球菌神经氨酸酶有抗性。在精浆样本中发现了来自其他来源的复合型寡糖，这表明对释放的聚糖进行分析存在误导风险。结果表明，如果将该分析应用于血清中以游离或复合形式特异性连接到PSA N-糖基化位点的寡糖，PSA上α2,3连接唾液酸的鉴定可能有助于区分恶性与良性疾病。
