Gene expression alterations in formalin-fixed, paraffin-embedded Barrett's esophagus and esophageal adenocarcinoma tissues

Botelho, Natalia K., Schneiders, Fiona I., Lord, Sarah J., Freeman, Araluen K., Tyagi, Sonika, Nancarrow, Derek J., Hayward, Nicholas K., Whiteman, David C. and Lord, Reginald V. N. (2010) Gene expression alterations in formalin-fixed, paraffin-embedded Barrett's esophagus and esophageal adenocarcinoma tissues. Cancer Biology Therapy, 10 2: 172-179. doi:10.4161/cbt.10.2.12166

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Author Botelho, Natalia K.
Schneiders, Fiona I.
Lord, Sarah J.
Freeman, Araluen K.
Tyagi, Sonika
Nancarrow, Derek J.
Hayward, Nicholas K.
Whiteman, David C.
Lord, Reginald V. N.
Title Gene expression alterations in formalin-fixed, paraffin-embedded Barrett's esophagus and esophageal adenocarcinoma tissues
Journal name Cancer Biology Therapy   Check publisher's open access policy
ISSN 1538-4047
Publication date 2010-07-15
Sub-type Article (original research)
DOI 10.4161/cbt.10.2.12166
Volume 10
Issue 2
Start page 172
End page 179
Total pages 8
Place of publication United States
Publisher Landes Bioscience
Collection year 2011
Language eng
Formatted abstract
Background and aim:
Widespread applicability of tissue-based mRNA expression screening for Barrett's esophagus (BE) is likely to require (1) accurate methods for assaying archival formalin-fixed, paraffin-embedded (FFPE ) histopathology specimens taken at endoscopy, and (2) validation studies of promising biomarkers in different patient cohorts.

30 genes were significantly differentially expressed by histopathology tissue type. The direction and magnitude of the differences were very similar to those found in previous studies using fresh frozen tissues. Novel upregulated genes were TSPA N8 (also known as CO-029), TSPA N24 (CD151), EGR1 and TCIRG1. Novel downregulated genes were DPYD, TSPA N29 (CD9) and Ets1. Strong associations between histopathology type and gene expression were observed with the overexpressed genes: cyclo-oxygenase-2 (COX-2), for which histopathology type explained 77.7% of the variation in expression, TSPA N1 (73.5%), TSPA N8 (62.9%), SPA RC (62.1%), MMP7 (50.8%); and the under-expressed genes ADH7 (53.7%), AP C (58.2%), RAR-gamma (51.3%).

mRNA was isolated from 54 FFPE small endoscopic biopsies from patients with Barrett's intestinal metaplasia (BE), esophageal adenocarcinoma (EA C), or control patients with a normal squamous-lined esophagus. Multiplexed tandem PCR (MT-PCR) was used to quantitate 50 selected candidate genes for BE and control genes in duplicate. Principal component analysis (PCA) was conducted to explore the presence of global differences in gene expression profiles. Oneway analysis of variance (ANOVA) of the transformed data was used to identify genes that were differentially expressed between different histological subtypes. Differentially expressed genes with a fold change of ≥2 (upregulated) or ≤-2 (downregulated) are reported with the p value for each comparison (EA C vs. normal, EA C vs. BE and BE vs. normal). The Benjamini-Hochberg method was used to control the false discovery rate at 0.01 for all comparisons.


Alterations in expression of select genes are strongly associated with BE or EA C or both. This study's findings for many highly differentially expressed genes are very similar to those previously reported, suggesting that these genes should be tested further in longitudinal studies for their potential role as biomarkers of progression to more advanced Barrett's disease. © 2010 Landes Bioscience.
Keyword Barrett's esophagus
Esophageal adenocarcinoma
Esophageal neoplasms
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Medicine Publications
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Created: Wed, 23 Mar 2011, 12:55:37 EST by Lisa Hennell on behalf of School of Medicine