TITLE

EXPRESSION ANALYSIS OF THE METAPLASIA DYSPLASIA CARCINOMA SEQUENCE IN BARRETT'S OESOPHAGUS AND ADENOCARCINOMA

AUTHOR(S)
Penman, I.D.; Smith, V.; Shen, E.F.; Wieand, D.; Landon, T.H.; Wong, N.A.C.S.; Lessells, A.M.; Paterson-Brown, S.; Tang, J.Z.; Wu, T.; Hillan, K.J.
PUB. DATE
April 2003
SOURCE
Gut;Apr2003 Supplement 1, Vol. 52, pA7
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Introduction and Aims: The molecular genetic events involved in the metaplasia dysplasia carcinoma (MDC) sequence in Barrett's oesophagus (CLO) are incompletely understood. We applied microarray expression analysis of endoscopic biopsies to study further these events and to detect novel genes involved in the process. Methods: Paired biopsies representing progression through Barrett's oesophagus (CLO), Iow and high-grade dysplasia (LGD, HGD), odenocarcinoma (Adca), and CLO adjacent to adenocarcinoma (Adca-BO), were taken from patients undergoing surveillance endoscopy. Biopsies were also taken from normal squamous mucosa. cDNA microarrays of 9031 genes were used to identify genes that were expressed in different disease stages. Data for each microarray were normalised to calculate Z scores and expression ratios: genes with Z scores > 1.7 (ratios 2-20) occurring in > 25% of samples from each "stage" were considered to be significantly expressed. Results: 460 genes satisfied these criteria. The mean number of expressed markers increased with progression from CLO (7.6) through LGD (11.7) to HGD (16.4). The data reveal progressive increases with dysplasia in a variety of markers involved in inflammation (eg IL-1 homologue H1, IL-17 and its receptor, chemokine receptor CXCR4, COX-2), intestinal differentiation (eg myosin MY01A, AGR2) and carcinogenesis (eg c-fos, EGFR, VEGFC), suggestive of a differentiated small intestinal enterocyte lineage, along with increased expression of TCF4. Gene expression profiles in adenocarcinoma also show evidence of Wnt-related expression, similar to colonic carcinoma. Conclusions: These results define a collection of markers that may assist in identifying patients with higher risk of developing cancer, and highlight multiple novel genes that merit further study in Barrett's.
ACCESSION #
9747296

 

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