Association of decreased expressions of α1,6-fucosyltransferase (α1,6-FT), GDP-mannose-4,6-dehydratase (GMD), and GDP-fucose transporter (GDP-Fuc Tr) with squamous histology in non-small cell lung cancers (NSCLCs).

Abstract

e17520 Background: α1,6-FT, a key enzyme for the core fucosylation of N-glycans, has been shown to be needed for the function of EGF and TGF-β1 receptors. α1,6-FT expression is found in human normal bronchial epithelial cells and bronchial gland cells. However, α1,6-FT expression has not been previously examined in NSCLCs. GMD generates GDP-fucose from GDP-mannose, and is imperative for the synthesis of all fucosylated oligosaccharides. GDP-fucose is transported into the Golgi apparatus by GDP-Fuc Tr to serve as a substrate of FTs. Methods: We examined expressions of α1,6-FT, GMD and GDP-Fuc Tr by immunohistochemistry in 156 surgically resected NSCLCs. Results: High, moderate and low expression of α1,6-FT was found in 25 (16.0%), 35 (22.4%) and 96 (61.6%) NSCLCs, respectively. Multivariate logistic regression analysis for the correlation between α1,6-FT expression and various characteristics revealed a significant association between low α1,6-FT expression and squamous cell carcinomas, as compared with non-squamous cell carcinomas (low vs. moderate, p = 0.0005; low vs. high, p = 0.005). High, moderate and low expression of GMD was found in 32 (20.5%), 32 (20.5%) and 92 (59.0%) NSCLCs, respectively. Multivariate logistic regression analysis for the correlation between GMD expression and various characteristics revealed a significant association between low GMD expression and squamous cell carcinomas, as compared with non-squamous cell carcinomas (low vs. moderate, p = 0.005; low vs. high, p = 0.02). Low expression of α1,6-FT was more prevalent in tumors with low GMD expression than in those with moderate or high GMD expression (p = 0.002). High/moderate, low and no expression of GDP-Fuc Tr was found in 7 (4.5%), 23 (14.7%) and 126 (80.8%) NSCLCs, respectively. Low GDP-Fuc Tr expression was significantly more prevalent in squamous cell carcinomas compared with non-squamous cell carcinomas (p = 0.003). Conclusions: These results indicate that α1,6-FT, GMD and GDP-Fuc Tr may be new markers of NSCLCs with specificity for histology.