Altered gene expression of folate enzymes in adjacent mucosa is associated with outcome of colorectal cancer patients.

PURPOSE: The purpose of this study was to analyze whether gene expression levels of folate enzymes in adjacent mucosa were associated with outcome of colorectal cancer patients. EXPERIMENTAL DESIGN: Real-time PCR was used to quantify expression levels of folate-associated genes including the reduced folate carrier (RFC-1), folylpolyglutamate synthase (FPGS), gamma-glutamyl hydrolase (GGH),and thymidylate synthase (TS) in tumor tissue and adjacent mucosa of patients with primary colorectal cancer (n=102). Furthermore, reduced folates in the tissues were measured with a binding-assay method. RESULTS: Mean gene expression levels of RFC-1, FPGS, GGH, and TS were significantly higher in tumor biopsies compared with mucosa. Univariate and multivariate analyses showed that the FPGS gene expression level in mucosa, but not in tumor, was a prognostic parameter independent of the clinicopathological factors with regard to survival. Patients with high FPGS levels (>0.92) in mucosa also showed significantly higher total folate concentrations (P=0.03) and gene expression levels of RFC-1 (