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
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- dc.contributor.author Dyrskjøt, Larsca
- dc.contributor.author Reinert, Thomasca
- dc.contributor.author Novoradovsky, Alexeyca
- dc.contributor.author Zuiverloon, Tahlita CMca
- dc.contributor.author Beukers, Willemienca
- dc.contributor.author Zwarthoff, Ellenca
- dc.contributor.author Malats i Riera, Núriaca
- dc.contributor.author Real, Francisco X.ca
- dc.contributor.author Segersten, Ulrikaca
- dc.contributor.author Malmström, Per-Unoca
- dc.contributor.author Knowles, Meganca
- dc.contributor.author Hurst, Carolynca
- dc.contributor.author Sorge, Josephca
- dc.contributor.author Borre, Michaelca
- dc.date.accessioned 2015-06-02T08:11:23Z
- dc.date.available 2015-06-02T08:11:23Z
- dc.date.issued 2012ca
- dc.description.abstract 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.en
- dc.description.sponsorship 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.en
- dc.format.mimetype application/pdfca
- dc.identifier.citation Dyrskjot L, Reinert T, Novoradovsky A, Zuiverloon TCM, Beukers W, Zwarthoff E et al. 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. British Journal of Cancer. 2012; 107: 1392-1398. DOI 10.1038/bjc.2012.412ca
- dc.identifier.doi http://dx.doi.org/10.1038/bjc.2012.412
- dc.identifier.issn 0007-0920ca
- dc.identifier.uri http://hdl.handle.net/10230/23714
- dc.language.iso engca
- dc.publisher Cancer Research UKca
- dc.relation.ispartof British Journal of Cancer. 2012;107:1392-8
- dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/201663
- dc.rights From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License.en
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.rights.uri http://creativecommons.org/licenses/by-nc-sa/3.0/
- dc.subject.keyword Bladder canceren
- dc.subject.keyword PCRen
- dc.subject.keyword Heterogeneityen
- dc.subject.keyword Outcomees
- dc.subject.keyword Progressionen
- dc.subject.other Bufeta -- Càncer -- Aspectes molecularsca
- dc.subject.other Prognosica
- dc.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 PCRen
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/publishedVersionca