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E-GEOD-36223 - Molecular defense mechanisms of Barrett's metaplasia estimated by an integrative genomics

Status
Released on 8 March 2012, last updated on 27 June 2012
Organism
Homo sapiens
Samples (46)
Array (1)
Protocols (6)
Description
Barrett's esophagus is characterized by the replacement of squamous epithelium with specialized intestinal metaplastic mucosa. The exact mechanisms of initiation and development of Barrett's metaplasia remain unknown, but a hypothesis of successful adaptation against noxious reflux components has been proposed. To search for the repertoire of adaptation mechanisms of Barrett's metaplasia, we employed high-throughput functional genomic and proteomic methods that defined the molecular background of metaplastic mucosa resistance to reflux. Transcriptional profiling was established for 23 pairs of esophageal squamous epithelium and Barrett's metaplasia tissue samples using Affymetrix U133A 2.0 GeneChips and validated by quantitative real-time polymerase chain reaction. Differences in protein composition were assessed by electrophoretic and mass-spectrometry-based methods. Among 2,822 genes differentially expressed between Barrett's metaplasia and squamous epithelium, we observed significantly overexpressed metaplastic mucosa genes that encode cytokines and growth factors, constituents of extracellular matrix, basement membrane and tight junctions, and proteins involved in prostaglandin and phosphoinositol metabolism, nitric oxide production, and bioenergetics. Their expression likely reflects defense and repair responses of metaplastic mucosa, whereas overexpression of genes encoding heat shock proteins and several protein kinases in squamous epithelium may reflect lower resistance of normal esophageal epithelium than Barrett's metaplasia to reflux components. Despite the methodological and interpretative difficulties in data analyses discussed in this paper, our studies confirm that Barrett's metaplasia may be regarded as a specific microevolution allowing for accumulation of mucosal morphological and physiological changes that better protect against reflux injury. Department of Gastroenterology, Medical Center for Postgraduate Education and Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781 Warsaw, Poland 2 types of tissue sample derived from the same patient: > Normal squamous epithelium (NE) from patients with longsegment of Barret’s epithelium > Metaplastic epithelium from Barrett’s esophagus (BE)
Experiment type
transcription profiling by array 
Contacts
Krzysztof Goryca <geo@ncbi.nlm.nih.gov>, Eugeniusz Butruk, Jakub Karczmarski, Jarosław Reguła, Jerzy Ostrowski, Lucjan S Wyrwicz, Michał Dadlez, Michał Mikula, Paweł Gaj, Piotr Brągoszewski, Tymon Rubel
Citation
Molecular defense mechanisms of Barrett's metaplasia estimated by an integrative genomics. Ostrowski J, Mikula M, Karczmarski J, Rubel T, Wyrwicz LS, Bragoszewski P, Gaj P, Dadlez M, Butruk E, Regula J. , PMID:17415542
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-36223.idf.txt
Sample and data relationshipE-GEOD-36223.sdrf.txt
Raw data (2)E-GEOD-36223.raw.1.zip, E-GEOD-36223.raw.2.zip
Processed data (1)E-GEOD-36223.processed.1.zip
Array designA-AFFY-37.adf.txt
R ExpressionSetE-GEOD-36223.eSet.r
Links