Ishimura Hirofumi, Takahashi Toshiko, Nakagawa Hiroaki, Nishimura Shin-Ichiro, Arai Yoichi, Horikawa Yohei, Habuchi Tomonori, Miyoshi Eiji, Kyan Atsushi, Hagisawa Shigeru, Ohyama Chikara
Department of Urology, Hirosaki University School of Medicine, Hirosaki, Japan.
Clin Cancer Res. 2006 Apr 15;12(8):2506-11. doi: 10.1158/1078-0432.CCR-05-1938.
N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes beta1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins. We examined the relationship between GnT-V expression and clinicopathologic features of the patients with bladder cancer.
We immunohistochemically examined GnT-V expression in paraffin-embedded bladder cancer specimen using anti-GnT-V monoclonal antibody. We compared GnT-V expression with cause-specific survival of the patients with bladder cancer treated by radical cystectomy. Kaplan-Meier survival curves were generated to show the cause-specific survival. Univariate and multivariate analyses were carried out to compare GnT-V expression with other clinical and pathologic variables. We also evaluated mRNA expression of GnT-V and N-linked oligosaccharide structure in bladder cancer specimens.
Immunohistochemistry revealed that GnT-V expression inversely correlated with tumor grade and stage. The incidence of positive GnT-V expression in bladder cancer was significantly higher in low-grade/superficial cancer than in high-grade/invasive cancer. The patients whose tumor was positive for GnT-V survived significantly longer than those whose tumor was negative for GnT-V. Univariate and multivariate analyses revealed that GnT-V expression was an independent predictor of prognosis of the patient. The expression of GnT-V mRNA determined by reverse transcription-PCR was consistent with the results with immunohistochemistry for tumor samples. Carbohydrate structural analysis revealed that superficial bladder cancer is rich in branched N-linked oligosaccharides, for which biosynthesis GnT-V is responsible.
GnT-V and its resultant beta1-6 branching N-linked oligosaccharides are closely related to low malignant potential and good prognosis of the patients with bladder cancer.
N-乙酰葡糖胺基转移酶V（GnT-V）是一种催化细胞蛋白天冬酰胺（N）连接寡糖（N-聚糖）上N-乙酰葡糖胺β1-6分支的酶。我们研究了GnT-V表达与膀胱癌患者临床病理特征之间的关系。
我们使用抗GnT-V单克隆抗体，对石蜡包埋的膀胱癌标本进行免疫组织化学检测GnT-V表达。我们将GnT-V表达与接受根治性膀胱切除术的膀胱癌患者的病因特异性生存率进行比较。绘制Kaplan-Meier生存曲线以显示病因特异性生存率。进行单因素和多因素分析，以比较GnT-V表达与其他临床和病理变量。我们还评估了膀胱癌标本中GnT-V的mRNA表达和N-连接寡糖结构。
免疫组织化学显示，GnT-V表达与肿瘤分级和分期呈负相关。低级别/浅表性癌中GnT-V表达阳性的发生率显著高于高级别/浸润性癌。肿瘤GnT-V阳性的患者比肿瘤GnT-V阴性的患者存活时间显著更长。单因素和多因素分析显示，GnT-V表达是患者预后的独立预测指标。通过逆转录-PCR测定的GnT-V mRNA表达与肿瘤样本的免疫组织化学结果一致。碳水化合物结构分析显示，浅表性膀胱癌富含分支N-连接寡糖，其生物合成由GnT-V负责。
GnT-V及其产生的β1-6分支N-连接寡糖与膀胱癌患者的低恶性潜能和良好预后密切相关。
