alpha-2,3-Sialyltransferase type 3N and alpha-1,3-fucosyltransferase type VII are related to sialyl Lewis(x) synthesis and patient survival from lung carcinoma

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.