N-acetylglucosaminyltransferase V and beta1-6 branching N-linked oligosaccharides are associated with good prognosis of patients with bladder cancer.

Abstract

PURPOSE:

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.

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 beta1-6 branching N-linked oligosaccharides are closely related to low malignant potential and good prognosis of the patients with bladder cancer.

• Authors: Hirofumi Ishimura, Toshiko Takahashi, Hiroaki Nakagawa, Shin-Ichiro Nishimura, Yoichi Arai, Yohei Horikawa, Tomonori Habuchi, Eiji Miyoshi, Atsushi Kyan, Shigeru Hagisawa, Chikara Ohyama
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 12 Issue 8 Pg. 2506-11 (Apr 15 2006) ISSN: 1078-0432 [Print] United States
• PMID: 16638859 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• beta-Glucans
• beta-1,6-glucan
• N-Acetylglucosaminyltransferases
• alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase

Topics

• Adult
• Aged
• Aged, 80 and over
• Chromatography, High Pressure Liquid
• Female
• Gene Expression Regulation, Enzymologic
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Multivariate Analysis
• N-Acetylglucosaminyltransferases (genetics, metabolism)
• Prognosis
• RNA, Messenger (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Survival Analysis
• Urinary Bladder Neoplasms (metabolism, pathology)
• beta-Glucans (chemistry, metabolism)