Journal of Gastroenterology

, Volume 49, Issue 4, pp 702–714

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
    • Department of Surgery, Institute of GastroenterologyTokyo Women’s Medical University
  • Hiroaki Sugiyama
    • Department of Gastroenterology, Division of Biomedical Science, Faculty of MedicineUniversity of Tsukuba
  • Kazunori Ishige
    • Department of Gastroenterology, Division of Biomedical Science, Faculty of MedicineUniversity of Tsukuba
  • Toru Kawamoto
    • Department of Surgery, Institute of GastroenterologyTokyo Women’s Medical University
  • Takehiro Ota
    • Department of Surgery, Institute of GastroenterologyTokyo Women’s Medical University
  • Shunichi Ariizumi
    • Department of Surgery, Institute of GastroenterologyTokyo Women’s Medical University
  • Masayuki Yamato
    • Institute of Advanced Biomedical Engineering and ScienceTokyo Women’s Medical University
  • Shinichi Kadota
    • Department of Infection Biology, Division of Biomedical Science, Faculty of MedicineUniversity of Tsukuba
  • Kaoru Takeuchi
    • Department of Infection Biology, Division of Biomedical Science, Faculty of MedicineUniversity of Tsukuba
  • Akiko Ishikawa
    • Division of Health SciencesOsaka University Graduate School of Medicine
  • Masafumi Onodera
    • Department of GeneticsNational Research Institute for Child Health and Development
  • Kojiro Onizawa
    • Department of Oral and Maxillofacial Surgery, Division of Biomedical Science, Faculty of MedicineUniversity of Tsukuba
  • Masakazu Yamamoto
    • Department of Surgery, Institute of GastroenterologyTokyo Women’s Medical University
  • Eiji Miyoshi
    • Division of Health SciencesOsaka University Graduate School of Medicine
    • Medical Science, Division of Clinical Science, Faculty of MedicineUniversity of Tsukuba
Original Article—Liver, Pancreas, and Biliary Tract

DOI: 10.1007/s00535-013-0813-2

Cite this article as:
Onuki, K., Sugiyama, H., Ishige, K. et al. J Gastroenterol (2014) 49: 702. doi:10.1007/s00535-013-0813-2

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

Gallbladder carcinomaN-Acetylglucosaminyltransferase VMalignant behaviorPostsurgical prognosisTumor cell biology

Abbreviations

mAb

Monoclonal antibody

GalNAc-T

N-acetylgalactosaminyltransferase

GnT-V

N-acetylglucosaminyltransferase

pT

Pathological tumor stage

Copyright information

© Springer Japan 2013