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Expression of N-acetylglucosaminyltransferase V in the subserosal layer correlates with postsurgical survival of pathological tumor stage 2 carcinoma of the gallbladder
Authors:Kenichiro Onuki  Hiroaki Sugiyama  Kazunori Ishige  Toru Kawamoto  Takehiro Ota  Shunichi Ariizumi  Masayuki Yamato  Shinichi Kadota  Kaoru Takeuchi  Akiko Ishikawa  Masafumi Onodera  Kojiro Onizawa  Masakazu Yamamoto  Eiji Miyoshi  Junichi Shoda
Institution:1. Department of Surgery, Institute of Gastroenterology, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan
2. Department of Gastroenterology, Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
3. Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan
4. Department of Infection Biology, Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
5. Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
6. Department of Genetics, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo, Japan
7. Department of Oral and Maxillofacial Surgery, Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
8. Medical Science, Division of Clinical Science, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan
Abstract:

Background

N-Acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyzes the β1-6 branching of N-acetylglucosamine on asparagine-linked oligosaccharides of cellular proteins, enhances the malignant behaviors of carcinoma cells in experimental models. The aim of this study was to determine clinical significance of GnT-V expression in human pT2 gallbladder carcinoma with simple in vitro experiments.

Methods

Ninety patients with pT2 gallbladder carcinoma were included for this study. The in vitro and in vivo biological effects of GnT-V were investigated using gallbladder carcinoma cells with variable GnT-V expression levels induced by a small interfering RNA.

Results

Of the 90 cases, 57 showed positive staining and the remaining 33 demonstrated negative staining, the subcellular localization in the 57 cases was classified into the granular-type in 31 cases and the diffuse-type in 26 cases. In 76 cases with curative resection, postsurgical survival was significantly poorer in those showing positive staining than in those showing negative staining (P = 0.028). In all of the 76 cases, postsurgical recurrence was significantly more frequent in those showing diffuse-type localization than in those showing negative staining. Experimental analyses demonstrated that the down-regulation of GnT-V expression in gallbladder carcinoma cells induced suppression of cell growth in vitro. The expression levels of GnT-V in the cells were highly correlated with the rapid in vivo growth coupled with the enhanced angiogenesis, and the tendency to form liver metastasis.

Conclusions

GnT-V expression in the subserosal layer of pT2 gallbladder carcinoma is correlated with the aggressiveness of the disease.
Keywords:
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