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


METHODS
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.
Ishimura
Hirofumi
H
Department of Urology, Hirosaki University School of Medicine, Hirosaki, Japan.
Takahashi
Toshiko
T
Nakagawa
Hiroaki
H
Nishimura
Shin-Ichiro
S
Arai
Yoichi
Y
Horikawa
Yohei
Y
Habuchi
Tomonori
T
Miyoshi
Eiji
E
Kyan
Atsushi
A
Hagisawa
Shigeru
S
Ohyama
Chikara
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002851:Chromatography, High Pressure Liquid; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology*; D047071:beta-Glucans / Q000737:chemistry / Q000378:metabolism*
D012333:RNA, Messenger; D047071:beta-Glucans; C064197:beta-1,6-glucan; D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase