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CYR61 and TAZ Upregulation and Focal Epithelial to Mesenchymal Transition May Be Early Predictors of Barrett’s Esophagus Malignant Progression

2016-09-01Journal article Open access
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dc.contributor.authorCardoso, Joana
dc.contributor.authorMesquita, Marta
dc.contributor.authorDias Pereira, António
dc.contributor.authorBettencourt-Dias, Mónica
dc.contributor.authorChaves, Paula
dc.contributor.authorPereira-Leal, José B.
dc.date.accessioned2016-09-19T16:14:03Z
dc.date.available2016-09-19T16:14:03Z
dc.date.issued2016-09-01
dc.description.abstractBarrett'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.pt_PT
dc.description.sponsorshipOphiomics Precision Medicine.pt_PT
dc.identifier.citationCardoso 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.0161967pt_PT
dc.identifier.doi10.1371/journal.pone.0161967pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/696
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherPublic Library of Sciencept_PT
dc.relation.publisherversionhttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161967pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectBiomarkerspt_PT
dc.subjectImmunohistochemistry techniquespt_PT
dc.subjectBiopsypt_PT
dc.subjectGene expressionpt_PT
dc.subjectBarrett's esophaguspt_PT
dc.subjectDysplasiapt_PT
dc.subjectNuclear stainingpt_PT
dc.subjectRNA extractionpt_PT
dc.titleCYR61 and TAZ Upregulation and Focal Epithelial to Mesenchymal Transition May Be Early Predictors of Barrett’s Esophagus Malignant Progressionpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/HMSP-CT%2FSAU-ICT%2F0075%2F2009/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F26487%2F2006/PT
oaire.citation.endPage19pt_PT
oaire.citation.issue9pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titlePLoS ONEpt_PT
oaire.citation.volume11pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStreamSFRH
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication950d9933-b1f8-43c9-834b-36eda23788ff
relation.isProjectOfPublicationc837c6a8-5a3a-4a8b-91d3-04ee51b09478
relation.isProjectOfPublication.latestForDiscoveryc837c6a8-5a3a-4a8b-91d3-04ee51b09478

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