Altered gene expression of folate enzymes in adjacent mucosa is associated with outcome of colorectal cancer patients.
Journal article, 2003
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 (P<0.01), GGH (P<0.01), and TS (P=0.04) compared with patients with low FPGS levels. The total reduced folate concentration correlated with the gene expression levels of RFC-1 and FPGS but not with TS or GGH. CONCLUSION: Our results suggest that normal-appearing colonic mucosa adjacent to primary colon cancer can show altered gene expression levels of FPGS that may have bearing on the development of aggressive metastatic behavior of the tumor and on tumor-specific survival.
Gene Expression Regulation
Peptide Synthases
Prognosis
metabolism
Male
genetics
Thymidylate Synthase
metabolism
Survival Rate
Gene Expression Regulation
genetics
Enzymologic
Colon
enzymology
Humans
enzymology
secondary
metabolism
pathology
enzymology
metabolism
Reverse Transcriptase Polymerase Chain Reaction
Membrane Transport Proteins
genetics
pathology
metabolism
Neoplastic
Colorectal Neoplasms
genetics
Rectum
Folic Acid
Aged
genetics
Female
metabolism
genetics
Messenger
gamma-Glutamyl Hydrolase
RNA
Author
Elisabeth Odin
University of Gothenburg
Yvonne Wettergren
University of Gothenburg
Staffan Nilsson
University of Gothenburg
Chalmers, Department of Mathematical Statistics
Roger Willén
University of Gothenburg
Göran Carlsson
University of Gothenburg
C Paul Spears
Lars Larsson
University of Gothenburg
Bengt Gustavsson
University of Gothenburg
Clinical Cancer Research
1078-0432 (ISSN) 15573265 (eISSN)
Vol. 9 16 Pt 1 6012-9Subject Categories
MEDICAL AND HEALTH SCIENCES
PubMed
14676127