This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dosaka-Akita, H. Articles by Taniguchi, N. Search for Related Content PubMed PubMed Citation Articles by Dosaka-Akita, H. Articles by Taniguchi, N.

Expression of N-Acetylglucosaminyltransferase V Is Associated with Prognosis and Histology in Non-Small Cell Lung Cancers

¹ Department of Medical Oncology, Hokkaido University Graduate School of Medicine, Sapporo, Japan; ² Department of Biochemistry, Osaka University Medical School/Graduate School of Medicine, Suita, Japan; ³ First Department of Pathology, Fukushima Medical University, Fukushima, Japan; ⁴ Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan; and ⁵ Department of Surgical Oncology, Hokkaido University Graduate School of Medicine, Sapporo, Japan

Purpose: N-Acetylglucosaminyltransferase V (GnT-V), a key enzyme in the formation of branching of asparagine-linked oligosaccharides, is strongly linked to tumor invasion and metastasis of colon and breast cancers. However, GnT-V is expressed in many tissues, including normal lung. GnT-V expression has not been examined previously in human lung cancers. The objective of this study is to examine GnT-V expression in non-small cell lung cancers (NSCLCs) and to determine its relationship to biological and clinicopathological characteristics and prognosis.

Experimental Design: GnT-V expression was studied by immunohistochemistry in 217 surgically resected NSCLCs and analyzed statiscally in relation to various characteristics.

Results: High GnT-V expression was found in 113 (52.1%) NSCLCs, and low GnT-V expression was found in 104 (47.9%) NSCLCs. Multivariate logistic regression analysis revealed a significant association between low GnT-V expression and squamous cell carcinomas, as compared with nonsquamous cell carcinomas (P = 0.02). Among biological characteristics of tumors, Ki-67 labeling index was higher in tumors with low GnT-V expression than in those with high GnT-V expression, although this difference was not statistically significant (P = 0.09). Patients with tumors having low GnT-V expression had significantly shorter survival time than patients with tumors having high GnT-V expression in 103 patients with pStage I NSCLCs (5-year survival rates, 49% and 86%, respectively; P = 0.0009), as well as in 59 patients with pStage I non-squamous cell carcinomas (5-year survival rates, 54% and 89%, respectively; P = 0.007). Low GnT-V expression was a significant unfavorable prognostic factor in pStage I NSCLCs (hazard ratio, 2.86; P = 0.002) and in pStage I nonsquamous cell carcinomas (hazard ratio, 3.02; P = 0.02). Furthermore, ß1–6 branching of asparagine-linked oligosaccharides, which are products of GnT-V, were increased highly or moderately in 8 of 10 tumors with high GnT-V expression, as judged by leukoagglutinating phytohemagglutinin staining.

Conclusions: GnT-V expression is associated with histology in NSCLCs. Low GnT-V expression is associated with shorter survival and poor prognosis in pStage I overall NSCLCs and non-squamous cell carcinomas.

This article has been cited by other articles:

				O. Vagin, E. Tokhtaeva, I. Yakubov, E. Shevchenko, and G. Sachs Inverse Correlation between the Extent of N-Glycan Branching and Intercellular Adhesion in Epithelia: CONTRIBUTION OF THE Na,K-ATPase 1 SUBUNIT J. Biol. Chem., January 25, 2008; 283(4): 2192 - 2202. [Abstract] [Full Text] [PDF]

				H.-B. Guo, M. Randolph, and M. Pierce Inhibition of a Specific N-Glycosylation Activity Results in Attenuation of Breast Carcinoma Cell Invasiveness-related Phenotypes: INHIBITION OF EPIDERMAL GROWTH FACTOR-INDUCED DEPHOSPHORYLATION OF FOCAL ADHESION KINASE J. Biol. Chem., July 27, 2007; 282(30): 22150 - 22162. [Abstract] [Full Text] [PDF]

				L. W. Wattenberg An interlocker concept of carcinogenesis. Cancer Epidemiol. Biomarkers Prev., August 1, 2006; 15(8): 1425 - 1426. [Abstract] [Full Text] [PDF]

				H. Ishimura, T. Takahashi, H. Nakagawa, S.-I. Nishimura, Y. Arai, Y. Horikawa, T. Habuchi, E. Miyoshi, A. Kyan, S. Hagisawa, et al. N-Acetylglucosaminyltransferase V and {beta}1-6 Branching N-Linked Oligosaccharides Are Associated with Good Prognosis of Patients with Bladder Cancer Clin. Cancer Res., April 15, 2006; 12(8): 2506 - 2511. [Abstract] [Full Text] [PDF]

				S. F. Siddiqui, J. Pawelek, T. Handerson, C.-Y. Lin, R. B. Dickson, D. L. Rimm, and R. L. Camp Coexpression of {beta}1,6-N-Acetylglucosaminyltransferase V Glycoprotein Substrates Defines Aggressive Breast Cancers with Poor Outcome Cancer Epidemiol. Biomarkers Prev., November 1, 2005; 14(11): 2517 - 2523. [Abstract] [Full Text] [PDF]

				T. Handerson, R. Camp, M. Harigopal, D. Rimm, and J. Pawelek {beta}1,6-Branched Oligosaccharides Are Increased in Lymph Node Metastases and Predict Poor Outcome in Breast Carcinoma Clin. Cancer Res., April 15, 2005; 11(8): 2969 - 2973. [Abstract] [Full Text] [PDF]

				S.-i. Fukumoto, N. Yamauchi, H. Moriguchi, Y. Hippo, A. Watanabe, J. Shibahara, H. Taniguchi, S. Ishikawa, H. Ito, S. Yamamoto, et al. Overexpression of the Aldo-Keto Reductase Family Protein AKR1B10 Is Highly Correlated with Smokers' Non-Small Cell Lung Carcinomas Clin. Cancer Res., March 1, 2005; 11(5): 1776 - 1785. [Abstract] [Full Text] [PDF]