Altered gene expression of folate enzymes in adjacent mucosa is associated with outcome of colorectal cancer patients.
Artikel i vetenskaplig tidskrift, 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

Författare

Elisabeth Odin

Göteborgs universitet

Yvonne Wettergren

Göteborgs universitet

Staffan Nilsson

Göteborgs universitet

Chalmers, Institutionen för matematisk statistik

Roger Willén

Göteborgs universitet

Göran Carlsson

Göteborgs universitet

C Paul Spears

Lars Larsson

Göteborgs universitet

Bengt Gustavsson

Göteborgs universitet

Clinical Cancer Research

1078-0432 (ISSN)

Vol. 9 16 Pt 1 6012-9

Ämneskategorier

MEDICIN OCH HÄLSOVETENSKAP

PubMed

14676127

Mer information

Skapat

2017-10-07