J I Ogawa1, H Inoue, S Koide. 1. First Department of Surgery, School of Medicine, Tokai University, Japan.
Abstract
BACKGROUND: Biosynthesis of sialyl Lewis(x) (sLe(x)) requires a sialyltransferase for alpha-2,3-sialylation and a fucosyltransferase for alpha-1,3-fucosylation. To date, five human alpha-1,3-fucosyltransferase (Fuc-T) genes and five human alpha-2,3-sialyltransferase (ST) genes have been cloned. However, it is not known which enzyme is mainly responsible for sLe(x) synthesis. METHODS: Three hundred thirteen patients with nonsmall cell lung carcinoma who had a curative tumor resection were the subjects of this study. Using tumor tissues fixed in formaldehyde, amplification of genomic DNA of Fuc-T and ST was performed by PCR and correlated with sLe(x) staining and patient prognosis. RESULTS: The frequency of strong ST3N and Fuc-TVII amplification was significantly higher than that of STZ, ST4, Fuc-TIII, Fuc-TV, and Fuc-TVI amplification (P < 0.01). The frequency of sLe(x) staining was similar to ST3N and Fuc-TVII amplification. Survival of the patients whose tumors had strong amplification of both ST3N and Fuc-TVII was significantly shorter than that of patients whose tumors had no amplification of either gene (P < 0.01). In a multivariate analysis of survival, Fuc-TVII remained a statistically significant prognostic factor. CONCLUSIONS: In lung carcinoma, ST3N and Fuc-TVII may both be related to sLe(x) synthesis, and Fuc-TVII is a more important indicator of poor prognosis.
BACKGROUND: Biosynthesis of sialyl Lewis(x) (sLe(x)) requires a sialyltransferase for alpha-2,3-sialylation and a fucosyltransferase for alpha-1,3-fucosylation. To date, five humanalpha-1,3-fucosyltransferase (Fuc-T) genes and five human alpha-2,3-sialyltransferase (ST) genes have been cloned. However, it is not known which enzyme is mainly responsible for sLe(x) synthesis. METHODS: Three hundred thirteen patients with nonsmall cell lung carcinoma who had a curative tumor resection were the subjects of this study. Using tumor tissues fixed in formaldehyde, amplification of genomic DNA of Fuc-T and ST was performed by PCR and correlated with sLe(x) staining and patient prognosis. RESULTS: The frequency of strong ST3N and Fuc-TVII amplification was significantly higher than that of STZ, ST4, Fuc-TIII, Fuc-TV, and Fuc-TVI amplification (P < 0.01). The frequency of sLe(x) staining was similar to ST3N and Fuc-TVII amplification. Survival of the patients whose tumors had strong amplification of both ST3N and Fuc-TVII was significantly shorter than that of patients whose tumors had no amplification of either gene (P < 0.01). In a multivariate analysis of survival, Fuc-TVII remained a statistically significant prognostic factor. CONCLUSIONS: In lung carcinoma, ST3N and Fuc-TVII may both be related to sLe(x) synthesis, and Fuc-TVII is a more important indicator of poor prognosis.
Authors: Dhananjay D Marathe; E V Chandrasekaran; Joseph T Y Lau; Khushi L Matta; Sriram Neelamegham Journal: FASEB J Date: 2008-08-20 Impact factor: 5.191