Differential gene expression in normal esophagus and Barrett’s esophagus
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As the premalignant lesion of human esophageal adenocarcinoma (EAC), Barrett’s esophagus (BE) is characterized by intestinal metaplasia in the normal esophagus (NE). Gene expression profiling with microarray and serial analysis of gene expression (SAGE) may help us understand the potential molecular mechanism of human BE.
We analyzed three microarray datasets (two cDNA arrays and one oligonucleotide array) and one SAGE dataset with statistical tools, significance analysis of microarrays (SAM) and SAGE(Poisson), to identify individual genes differentially expressed in BE. Gene set enrichment analysis (GSEA) was used to identify a priori defined sets of genes that were differentially expressed. These gene sets were grouped according to either certain signaling pathways (GSEA curated), or the presence of consensus binding sequences of known transcription factors (GSEA motif). Immunohistochemical staining (IHC) was used to validate differential gene expression.
Both SAM and SAGE(Poisson) identified 68 differentially expressed genes (55 BE genes and 13 NE genes) with an arbitrary cutoff ratio (≥4-fold). With IHC on matched pairs of NE and BE tissues from 6 patients, these genes were grouped into 6 categories: category I (25 genes only expressed in BE), category II (5 genes only expressed in NE), category III (8 genes expressed more in BE than in NE), and category IV (2 genes expressed more in NE than in BE). Differential expression of the remaining genes was not confirmed by IHC either due to false discovery (category V), or lack of proper antibodies (category VI). Besides individual genes, the TGFβ pathway and several transcription factors (CDX2, HNF1, and HNF4) were identified by GSEA as enriched pathways and motifs in BE. Apart from 9 target genes known to be up-regulated in BE, IHC staining confirmed up-regulation of 19 additional CDX1 and CDX2 target genes in BE.
Our data suggested an important role of CDX1 and CDX2 in the development of BE. The IHC-confirmed gene list will lead to future studies on the molecular mechanism of BE.
- Differential gene expression in normal esophagus and Barrett’s esophagus
Journal of Gastroenterology
Volume 44, Issue 9 , pp 897-911
- Cover Date
- Print ISSN
- Online ISSN
- Springer Japan
- Additional Links
- Barrett’s esophagus
- Intestinal metaplasia
- Expression profile
- Industry Sectors
- Author Affiliations
- 1. Cancer Research Program, Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, 700 George Street, Durham, NC, 27707, USA
- 2. Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
- 3. Department of Biostatistics, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center/Biostatistics Shared Resource, Nashville, TN, 37232-2158, USA
- 4. Institute of Human Genetics, International Centre for Life, University of Newcastle upon Tyne, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK
- 5. Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA