Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCR

Background: Multiple clinical risk factors and genetic profiles have been demonstrated to predict progression of non-muscle invasive bladder cancer; however, no easily clinical applicable gene signature has been developed to predict disease progression independent of disease stage and grade. Methods...

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Autores: Dyrskjøt, Lars, Reinert, Thomas, Novoradovsky, Alexey, Zuiverloon, Tahlita CM, Beukers, Willemien, Zwarthoff, Ellen, Malats i Riera, Núria, Real, Francisco X., Segersten, Ulrika, Malmström, Per-Uno, Knowles, Megan, Hurst, Carolyn, Sorge, Joseph, Borre, Michael
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2012
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/23714
Acceso en línea:http://hdl.handle.net/10230/23714
http://dx.doi.org/10.1038/bjc.2012.412
Access Level:acceso abierto
Palabra clave:Bufeta -- Càncer -- Aspectes moleculars
Prognosi
Bladder cancer
PCR
Heterogeneity
Progression
Outcome
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spelling Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCRDyrskjøt, LarsReinert, ThomasNovoradovsky, AlexeyZuiverloon, Tahlita CMBeukers, WillemienZwarthoff, EllenMalats i Riera, NúriaReal, Francisco X.Segersten, UlrikaMalmström, Per-UnoKnowles, MeganHurst, CarolynSorge, JosephBorre, MichaelBufeta -- Càncer -- Aspectes molecularsPrognosiBladder cancerPCRHeterogeneityProgressionOutcomeBackground: Multiple clinical risk factors and genetic profiles have been demonstrated to predict progression of non-muscle invasive bladder cancer; however, no easily clinical applicable gene signature has been developed to predict disease progression independent of disease stage and grade. Methods: We measured the intra-patient variation of an 88-gene progression signature using 39 metachronous tumours from 17 patients. For delineation of the optimal quantitative reverse transcriptase PCR panel of markers, we used 115 tumour samples from patients in Denmark, Sweden, UK and Spain. Results: Analysis of intra-patient variation of the molecular markers showed 71% similar classification results. A final panel of 12 genes was selected, showing significant correlation with outcome. In multivariate Cox regression analysis, we found that the 12-gene signature was an independent prognostic factor (hazard ratio=7.4 (95% confidence interval: 3.4–15.9), P<0.001) when adjusting for stage, grade and treatment. Independent validation of the 12-gene panel and the determined cut-off values is needed and ongoing. Conclusion: Intra-patient marker variation in metachronous tumours is present. Therefore, to increase test sensitivity, it may be necessary to test several metachronous tumours from a patient’s disease course. A PCR-based 12-gene signature significantly predicts disease progression in patients with non-muscle invasive bladder cancer.The study was supported by The John and Birthe Meyer Foundation, the Danish Cancer Society, the Ministry of Technology and Science, and the Lundbeck Foundation. Furthermore, the research leading to these results has received funding from the European Community’s Seventh Framework program FP7/2007-2011 under grant agreement no. 201663.Cancer Research UK201520152012info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/23714http://dx.doi.org/10.1038/bjc.2012.412reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésBritish Journal of Cancer. 2012;107:1392-8info:eu-repo/grantAgreement/EC/FP7/201663From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License.http://creativecommons.org/licenses/by-nc-sa/3.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/237142026-06-12T07:21:37Z
dc.title.none.fl_str_mv Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCR
title Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCR
spellingShingle Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCR
Dyrskjøt, Lars
Bufeta -- Càncer -- Aspectes moleculars
Prognosi
Bladder cancer
PCR
Heterogeneity
Progression
Outcome
title_short Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCR
title_full Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCR
title_fullStr Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCR
title_full_unstemmed Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCR
title_sort Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCR
dc.creator.none.fl_str_mv Dyrskjøt, Lars
Reinert, Thomas
Novoradovsky, Alexey
Zuiverloon, Tahlita CM
Beukers, Willemien
Zwarthoff, Ellen
Malats i Riera, Núria
Real, Francisco X.
Segersten, Ulrika
Malmström, Per-Uno
Knowles, Megan
Hurst, Carolyn
Sorge, Joseph
Borre, Michael
author Dyrskjøt, Lars
author_facet Dyrskjøt, Lars
Reinert, Thomas
Novoradovsky, Alexey
Zuiverloon, Tahlita CM
Beukers, Willemien
Zwarthoff, Ellen
Malats i Riera, Núria
Real, Francisco X.
Segersten, Ulrika
Malmström, Per-Uno
Knowles, Megan
Hurst, Carolyn
Sorge, Joseph
Borre, Michael
author_role author
author2 Reinert, Thomas
Novoradovsky, Alexey
Zuiverloon, Tahlita CM
Beukers, Willemien
Zwarthoff, Ellen
Malats i Riera, Núria
Real, Francisco X.
Segersten, Ulrika
Malmström, Per-Uno
Knowles, Megan
Hurst, Carolyn
Sorge, Joseph
Borre, Michael
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Bufeta -- Càncer -- Aspectes moleculars
Prognosi
Bladder cancer
PCR
Heterogeneity
Progression
Outcome
topic Bufeta -- Càncer -- Aspectes moleculars
Prognosi
Bladder cancer
PCR
Heterogeneity
Progression
Outcome
description Background: Multiple clinical risk factors and genetic profiles have been demonstrated to predict progression of non-muscle invasive bladder cancer; however, no easily clinical applicable gene signature has been developed to predict disease progression independent of disease stage and grade. Methods: We measured the intra-patient variation of an 88-gene progression signature using 39 metachronous tumours from 17 patients. For delineation of the optimal quantitative reverse transcriptase PCR panel of markers, we used 115 tumour samples from patients in Denmark, Sweden, UK and Spain. Results: Analysis of intra-patient variation of the molecular markers showed 71% similar classification results. A final panel of 12 genes was selected, showing significant correlation with outcome. In multivariate Cox regression analysis, we found that the 12-gene signature was an independent prognostic factor (hazard ratio=7.4 (95% confidence interval: 3.4–15.9), P<0.001) when adjusting for stage, grade and treatment. Independent validation of the 12-gene panel and the determined cut-off values is needed and ongoing. Conclusion: Intra-patient marker variation in metachronous tumours is present. Therefore, to increase test sensitivity, it may be necessary to test several metachronous tumours from a patient’s disease course. A PCR-based 12-gene signature significantly predicts disease progression in patients with non-muscle invasive bladder cancer.
publishDate 2012
dc.date.none.fl_str_mv 2012
2015
2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/23714
http://dx.doi.org/10.1038/bjc.2012.412
url http://hdl.handle.net/10230/23714
http://dx.doi.org/10.1038/bjc.2012.412
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv British Journal of Cancer. 2012;107:1392-8
info:eu-repo/grantAgreement/EC/FP7/201663
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-sa/3.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/3.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cancer Research UK
publisher.none.fl_str_mv Cancer Research UK
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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