MicroRNA expression profiling in human Barrett's carcinogenesis

Matteo Fassan, Stefano Volinia, Jeff Palatini, Marco Pizzi, Raffaele Baffa, Marina De Bernard, Giorgio Battaglia, Paola Parente, Carlo M. Croce, Giovanni Zaninotto, Ermanno Ancona, Massimo Rugge

Research output: Contribution to journalArticle

Abstract

Barrett's esophagus (BE) is characterized by the native stratified squamous epithelium (N) lining the esophagus being replaced by a columnar epithelium with intestinal differentiation (Barrett's mucosa; BM). BM is considered as the main risk factor for esophageal adenocarcinoma (Barrett's adenocarcinoma; BAc). MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting messenger RNAs and they are reportedly dysregulated in BM. To test the hypothesis that a specific miRNA expression signature characterizes BM development and progression, we performed miRNA microarray analysis comparing native esophageal mucosa with all the phenotypic lesions seen in the Barrett's carcinogenic process. Specimens were collected from 14 BE patients who had undergone esophagectomy, including: 14 with N, 14 with BM, 7 with low-grade intraepithelial neoplasia, 5 with high-grade intra-epithelial neoplasia and 11 with BAc. Microarray findings were further validated by quantitive real-time polymerase chain reaction and in situ hybridization analyses using a different series of consecutive cases (162 biopsy samples and 5 esophagectomies) of histologically proven, long-segment BE. We identified a miRNA signature of Barrett's carcinogenesis consisting of an increased expression of 6 miRNAs and a reduced expression of 7 miRNAs. To further support these results, we investigated target gene expression using the Oncomine database and/or immunohistochemical analysis. We found that target gene expression correlated significantly with miRNA dysregulation. Specific miRNAs are directly involved in BE progression to cancer. miRNA profiling significantly expands current knowledge on the molecular history of Barrett's carcinogenesis, also identifying molecular markers of cancer progression.

Original languageEnglish
Pages (from-to)1661-1670
Number of pages10
JournalInternational Journal of Cancer
Volume129
Issue number7
DOIs
Publication statusPublished - Oct 1 2011

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Keywords

  • Barrett's esophagus
  • expression signature
  • gene target
  • miRNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Fassan, M., Volinia, S., Palatini, J., Pizzi, M., Baffa, R., De Bernard, M., Battaglia, G., Parente, P., Croce, C. M., Zaninotto, G., Ancona, E., & Rugge, M. (2011). MicroRNA expression profiling in human Barrett's carcinogenesis. International Journal of Cancer, 129(7), 1661-1670. https://doi.org/10.1002/ijc.25823