Upregulation of ornithine decarboxylase mRNA expression in Barrett's esophagus and Barrett's-associated adenocarcinoma.
The Barrett's multistage process is characterized histopathologically by progression from Barrett's intestinal metaplasia to Barrett's esophagus with dysplasia and ultimately adenocarcinoma. Understanding the cellular and molecular events in this multistage process may contribute to improved diagnosis and treatment. Ornithine decarboxylase (ODC) is the first enzyme in the biosynthesis of polyamines. Elevated ODC activity has been found to be associated with progression during Barrett's esophagus, but the regulation of ODC gene expression in the development of Barrett's-associated adenocarcinoma has not been reported. The aim of this study was to assess the prevalence and timing of ODC mRNA expression in the Barrett's metaplasia-dysplasia-adenocarcinoma sequence. ODC mRNA expression levels, relative to the stably expressed internal reference gene beta-actin, were measured using a quantitative reverse transcription-polymerase chain reaction (RT-PCR) method (ABI 7700 Sequence Detector System) in 104 specimens from 19 patients with Barrett's esophagus without carcinoma and 22 patients with Barrett's-associated adenocarcinoma. The median ODC mRNA expression levels were significantly increased in Barrett's esophagus tissues compared to matched normal tissues in patients without adenocarcinoma of the esophagus (P = 0.002; Wilcoxon test). A significant progressive increase in ODC mRNA expression was detectable through the stages of the metaplasia-dysplasia-carcinoma sequence in patients with Barrett's-associated adenocarcinoma (r = 0.719; P < or = 0.001; Spearman's rho test). These findings show that upregulation of ODC mRNA expression is an early event in the development and progression of Barrett's-associated adenocarcinoma of the esophagus, and they suggest that high ODC mRNA expression levels may be a clinically useful biomarker for the detection of occult adenocarcinoma
Brabender
J
J
Department of Biochemistry and Molecular Biology/Norris Comprehensive Cancer Research Center, University of Southern California Keck School of Medicine, Los Angeles, USA.
Lord
R V
RV
Danenberg
K D
KD
Metzger
R
R
Schneider
P M
PM
Uetake
H
H
Kawakami
K
K
Park
J M
JM
Salonga
D
D
Peters
J H
JH
DeMeester
T R
TR
Hölscher
A H
AH
Danenberg
P V
PV
D000230:Adenocarcinoma / Q000378:metabolism*; D000328:Adult; D000368:Aged; D001471:Barrett Esophagus / Q000378:metabolism*; D014408:Biomarkers, Tumor; D004938:Esophageal Neoplasms / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D009955:Ornithine Decarboxylase