Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.7/696
Título: CYR61 and TAZ Upregulation and Focal Epithelial to Mesenchymal Transition May Be Early Predictors of Barrett’s Esophagus Malignant Progression
Autor: Cardoso, Joana
Mesquita, Marta
Dias Pereira, António
Bettencourt-Dias, Mónica
Chaves, Paula
Pereira-Leal, José B.
Palavras-chave: Biomarkers
Immunohistochemistry techniques
Biopsy
Gene expression
Barrett's esophagus
Dysplasia
Nuclear staining
RNA extraction
Data: 1-Set-2016
Editora: Public Library of Science
Citação: Cardoso J, Mesquita M, Dias Pereira A, Bettencourt-Dias M, Chaves P, Pereira-Leal JB (2016) CYR61 and TAZ Upregulation and Focal Epithelial to Mesenchymal Transition May Be Early Predictors of Barrett ’ s Esophagus Malignant Progression. PLoS ONE 11(9): e0161967. doi:10.1371/journal.pone.0161967
Resumo: Barrett's esophagus is the major risk factor for esophageal adenocarcinoma. It has a low but non-neglectable risk, high surveillance costs and no reliable risk stratification markers. We sought to identify early biomarkers, predictive of Barrett's malignant progression, using a meta-analysis approach on gene expression data. This in silico strategy was followed by experimental validation in a cohort of patients with extended follow up from the Instituto Português de Oncologia de Lisboa de Francisco Gentil EPE (Portugal). Bioinformatics and systems biology approaches singled out two candidate predictive markers for Barrett's progression, CYR61 and TAZ. Although previously implicated in other malignancies and in epithelial-to-mesenchymal transition phenotypes, our experimental validation shows for the first time that CYR61 and TAZ have the potential to be predictive biomarkers for cancer progression. Experimental validation by reverse transcriptase quantitative PCR and immunohistochemistry confirmed the up-regulation of both genes in Barrett's samples associated with high-grade dysplasia/adenocarcinoma. In our cohort CYR61 and TAZ up-regulation ranged from one to ten years prior to progression to adenocarcinoma in Barrett's esophagus index samples. Finally, we found that CYR61 and TAZ over-expression is correlated with early focal signs of epithelial to mesenchymal transition. Our results highlight both CYR61 and TAZ genes as potential predictive biomarkers for stratification of the risk for development of adenocarcinoma and suggest a potential mechanistic route for Barrett's esophagus neoplastic progression.
Peer review: yes
URI: http://hdl.handle.net/10400.7/696
DOI: 10.1371/journal.pone.0161967
Versão do Editor: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161967
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Cardoso_PlosOne.(2016).PDFmain article2,36 MBAdobe PDFVer/Abrir
Cardoso_PlosOne.(2016)_SM_S1_Results.PDFsupplementary materials 1225,01 kBAdobe PDFVer/Abrir
Cardoso_PlosOne.(2016)_SM_S1_Table.XLSXsupplementary materials 29,72 kBMicrosoft Excel XMLVer/Abrir
Cardoso_PlosOne.(2016)_SM_S2_Fig.PDFsupplementary materials 3442,74 kBAdobe PDFVer/Abrir
Cardoso_PlosOne.(2016)_SM_S2_Table.XLSXsupplementary materials 48,73 kBMicrosoft Excel XMLVer/Abrir
Cardoso_PlosOne.(2016)_SM_S3_Fig.PDFsupplementary materials 5365,91 kBAdobe PDFVer/Abrir
Cardoso_PlosOne.(2016)_SM_S3_Table.XLSXsupplementary materials 6129,92 kBMicrosoft Excel XMLVer/Abrir
Cardoso_PlosOne.(2016)_SM_S4_Fig.PDFsupplementary materials 7111,33 kBAdobe PDFVer/Abrir
Cardoso_PlosOne.(2016)_SM_S4_Table.XLSXsupplementary materials 817,61 kBMicrosoft Excel XMLVer/Abrir
Cardoso_PlosOne.(2016)_SM_S5_Fig.PDFsupplementary materials 9490,28 kBAdobe PDFVer/Abrir
Cardoso_PlosOne.(2016)_SM_S5_Table.XLSXsupplementary materials 1032,12 kBMicrosoft Excel XMLVer/Abrir
Cardoso_PlosOne.(2016)_SM_S6_Fig.PDFsupplementary materials 11433,21 kBAdobe PDFVer/Abrir
Cardoso_PlosOne.(2016)_SM_S6_Table.XLSXsupplementary materials 1227,76 kBMicrosoft Excel XMLVer/Abrir
Cardoso_PlosOne.(2016)_SM_S7_Fig.PDFsupplementary materials 13661,47 kBAdobe PDFVer/Abrir


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