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Type: Journal article
Title: Whole genome expression array profiling highlights differences in mucosal defense genes in Barrett's esophagus and esophageal adenocarcinoma
Author: Nancarrow, D.
Clouston, A.
Smithers, B.
Gotley, D.
Drew, P.
Watson, D.
Tyagi, S.
Hayward, N.
Whiteman, D.
Citation: PLoS One, 2011; 6(7):1-15
Publisher: Public Library of Science
Issue Date: 2011
ISSN: 1932-6203
Statement of
Derek J. Nancarrow, Andrew D. Clouston, B. Mark Smithers, David C. Gotley, Paul A. Drew, David I. Watson, Sonika Tyagi, Nicholas K. Hayward, David C. Whiteman, for the Australian Cancer Study and the Study of Digestive Health
Abstract: Esophageal adenocarcinoma (EAC) has become a major concern in Western countries due to rapid rises in incidence coupled with very poor survival rates. One of the key risk factors for the development of this cancer is the presence of Barrett's esophagus (BE), which is believed to form in response to repeated gastro-esophageal reflux. In this study we performed comparative, genome-wide expression profiling (using Illumina whole-genome Beadarrays) on total RNA extracted from esophageal biopsy tissues from individuals with EAC, BE (in the absence of EAC) and those with normal squamous epithelium. We combined these data with publically accessible raw data from three similar studies to investigate key gene and ontology differences between these three tissue states. The results support the deduction that BE is a tissue with enhanced glycoprotein synthesis machinery (DPP4, ATP2A3, AGR2) designed to provide strong mucosal defenses aimed at resisting gastro-esophageal reflux. EAC exhibits the enhanced extracellular matrix remodeling (collagens, IGFBP7, PLAU) effects expected in an aggressive form of cancer, as well as evidence of reduced expression of genes associated with mucosal (MUC6, CA2, TFF1) and xenobiotic (AKR1C2, AKR1B10) defenses. When our results are compared to previous whole-genome expression profiling studies keratin, mucin, annexin and trefoil factor gene groups are the most frequently represented differentially expressed gene families. Eleven genes identified here are also represented in at least 3 other profiling studies. We used these genes to discriminate between squamous epithelium, BE and EAC within the two largest cohorts using a support vector machine leave one out cross validation (LOOCV) analysis. While this method was satisfactory for discriminating squamous epithelium and BE, it demonstrates the need for more detailed investigations into profiling changes between BE and EAC.
Keywords: Australian Cancer Study
Study of Digestive Health
Mucous Membrane
Carcinoma, Squamous Cell
Esophageal Neoplasms
Barrett Esophagus
RNA, Messenger
Oligonucleotide Array Sequence Analysis
Case-Control Studies
Gene Expression Profiling
Reverse Transcriptase Polymerase Chain Reaction
Cell Proliferation
Genome, Human
Aged, 80 and over
Middle Aged
Young Adult
Biomarkers, Tumor
Support Vector Machine
Description: Extent: 15p.
Rights: © 2011 Nancarrow et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI: 10.1371/journal.pone.0022513
Grant ID: ARC
Appears in Collections:Aurora harvest
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