α1,2-Fucosylated and β-N-acetylgalactosaminylated prostate-specific antigen as an efficient marker of prostatic cancer
α1,2-Fucosylated and β-N-acetylgalactosaminylated prostate-specific antigen as an efficient marker of prostatic cancer
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DOI：
10.1093/glycob/cwp197
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发表时间：
2010-04-01
期刊：
影响因子：
4.3
通讯作者：
Yamashita, Katsuko
中科院分区：
文献类型：
--
作者：
Fukushima, Keiko;Satoh, Takefumi;Yamashita, Katsuko
前列腺特异性抗原（PSA）因其高度特异性而被广泛用作前列腺癌（PC）的诊断标志物。然而，血清PSA升高不仅发生在PC中，也发生在良性前列腺增生（BPH）中。由于N-聚糖在致癌过程中的结构变化是常见的现象，我们研究了PC特异性N-聚糖是否与PSA相关。我们首先分析了PSA的糖结构来自精液，BPH和PC患者的血清，和PC细胞系，即，LNCaP使用八个凝集素固定柱，然后用酶联免疫吸附测定（ELISA）。前列腺癌患者血清PSA的部分结合到Fuc α 1-2Gal和β GalNAc结合天花粉凝集素-II（TJA-II）柱，而前列腺增生患者血清PSA的部分没有表现出这种结合能力，从而暗示在癌发生过程中PSA的α 1，2-岩藻糖基化和β-N-乙酰半乳糖胺化的表达升高。然后，我们进行了实时聚合酶链反应（PCR），并证实这些结构变化是负责岩藻糖基转移酶I（FUT 1）和β-N-乙酰半乳糖胺转移酶4（B4 GALNT 4）的表达升高。第二，我们测定了40例前列腺癌和前列腺增生患者血清PSA中TJA-II结合的PSA含量和TJA-II柱层析结合率。结果表明，TJA-II结合的PSA含量和TJA-II结合率（%）均能以95%以上的概率区分PC和BPH，TJA-II结合的PSA可作为PC的潜在标志物。
A prostate-specific antigen (PSA) is widely used as a diagnostic marker for prostate cancer (PC) because of its high specificity. However, elevated serum PSA does not occur only in PC but also in benign prostatic hyperplasia (BPH). Since the structural changes of N-glycans during carcinogenesis are common phenomena, we investigated whether PC-specific N-glycans are linked to PSA. We first analyzed the carbohydrate structures of PSA derived from seminal fluid, serum of BPH and PC patients, and PC cell line, namely, LNCaP using eight lectin-immobilized columns and then with enzyme-linked immunosorbent assay (ELISA). The fraction of serum PSA from PC patients bound to both Fuc alpha 1-2Gal and beta GalNAc binding Trichosanthes japonica agglutinin-II (TJA-II) column, while that from BPH patients did not exhibit this binding ability, thereby implying that there is elevated expression of alpha 1,2-fucosylation and beta-N-acetylgalactosaminylation of PSA during carcinogenesis. We then performed a real-time polymerase chain reaction (PCR) and confirmed that these structural changes were responsible for the elevated expression of fucosyltransferase I (FUT1) and beta-N-acetylgalactosaminyltransferase 4(B4GALNT4). Second, we measured TJA-II-bound PSA contents and the binding ratios of TJA-II column chromatography in serum PSA samples from 40 patients of both PC and BPH. The results indicated that both TJA-II-bound PSA content and TJA-II binding ratios (%) could be used to discriminate between PC and BPH with more than 95% probability, and TJA-II-bound PSA can be regarded as a potential marker of PC.