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N-Acetylglucosaminyltransferase V and ß1-6 Branching N-Linked Oligosaccharides Are Associated with Good Prognosis of Patients with Bladder Cancer

Authors' Affiliations: ¹ Department of Urology, Hirosaki University School of Medicine, Hirosaki, Japan; ² Department of Clinical Laboratory, Tohoku University Hospital; ³ Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan; ⁴ Division of Biological Science, Graduate School of Sciences, Hokkaido University, Sapporo, Japan; ⁵ Department of Urology, Akita University School of Medicine, Akita, Japan; and ⁶ Department of Biochemistry, Osaka University Graduate School of Medicine, Osaka, Japan

Requests for reprints: Chikara Ohyama, Department of Urology, Hirosaki University School of Medicine, 5 Zaifucho, Hirosaki 036-8562, Japan. Phone: 81-172-39-5091; Fax: 81-172-39-5092; E-mail: coyama{at}cc.hirosaki-u.ac.jp.

Purpose: N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes ß1-6 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.

Experimental Design: 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.

Results: 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.

Conclusions: GnT-V and its resultant ß1-6 branching N-linked oligosaccharides are closely related to low malignant potential and good prognosis of the patients with bladder cancer.