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Impact of Molecular...
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Seiler, RolandUniversity of Bern
(författare)
Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy
- Artikel/kapitelEngelska2017
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Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:943368a1-3e60-4232-8f4f-c719e983c28e
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https://lup.lub.lu.se/record/943368a1-3e60-4232-8f4f-c719e983c28eURI
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https://doi.org/10.1016/j.eururo.2017.03.030DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
Anmärkningar
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Background: An early report on the molecular subtyping of muscle-invasive bladder cancer (MIBC) by gene expression suggested that response to neoadjuvant chemotherapy (NAC) varies by subtype. Objective: To investigate the ability of molecular subtypes to predict pathological downstaging and survival after NAC. Design, setting, and participants: Whole transcriptome profiling was performed on pre-NAC transurethral resection specimens from 343 patients with MIBC. Samples were classified according to four published molecular subtyping methods. We developed a single-sample genomic subtyping classifier (GSC) to predict consensus subtypes (claudin-low, basal, luminal-infiltrated and luminal) with highest clinical impact in the context of NAC. Overall survival (OS) according to subtype was analyzed and compared with OS in 476 non-NAC cases (published datasets). Intervention: Gene expression analysis was used to assign subtypes. Outcome measurements and statistical analysis: Receiver-operating characteristics were used to determine the accuracy of GSC. The effect of GSC on survival was estimated by Cox proportional hazard regression models. Results and limitations: The models generated subtype calls in expected ratios with high concordance across subtyping methods. GSC was able to predict four consensus molecular subtypes with high accuracy (73%), and clinical significance of the predicted consensus subtypes could be validated in independent NAC and non-NAC datasets. Luminal tumors had the best OS with and without NAC. Claudin-low tumors were associated with poor OS irrespective of treatment regimen. Basal tumors showed the most improvement in OS with NAC compared with surgery alone. The main limitations of our study are its retrospective design and comparison across datasets. Conclusions: Molecular subtyping may have an impact on patient benefit to NAC. If validated in additional studies, our results suggest that patients with basal tumors should be prioritized for NAC. We discovered the first single-sample classifier to subtype MIBC, which may be suitable for integration into routine clinical practice. Patient summary: Different molecular subtypes can be identified in muscle-invasive bladder cancer. Although cisplatin-based neoadjuvant chemotherapy improves patient outcomes, we identified that the benefit is highest in patients with basal tumors. Our newly discovered classifier can identify these molecular subtypes in a single patient and could be integrated into routine clinical practice after further validation. Molecular subtypes in muscle-invasive bladder cancer appear have an impact on patient response to neoadjuvant chemotherapy (NAC); namely, patients with basal tumors showed the most benefit from NAC and should be prioritized for NAC. Moreover, these subtypes can be identified in a single sample by our discovered classifier.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Ashab, Hussam Al DeenGenomeDx Biosciences
(författare)
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Erho, NicholasGenomeDx Biosciences
(författare)
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van Rhijn, Bas W GAntoni Van Leeuwenhoek Hospital
(författare)
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Winters, BrianWashington University School of Medicine
(författare)
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Douglas, James JUniversity Hospital Southampton
(författare)
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van Kessel, Kim E MErasmus University Medical Center
(författare)
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Fransen van de Putte, Elisabeth E.Antoni Van Leeuwenhoek Hospital
(författare)
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Sommerlad, MatthewUniversity Hospital Southampton
(författare)
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Wang, Natalie Q.GenomeDx Biosciences
(författare)
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Choeurng, VoleakGenomeDx Biosciences
(författare)
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Gibb, Ewan A.GenomeDx Biosciences
(författare)
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Palmer-Aronsten, BeatrixGenomeDx Biosciences
(författare)
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Lam, Lucia L.GenomeDx Biosciences
(författare)
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Buerki, ChristineGenomeDx Biosciences
(författare)
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Davicioni, ElaiGenomeDx Biosciences
(författare)
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Sjödahl, GottfridLund University,Lunds universitet,Urologi - blåscancer, Malmö,Forskargrupper vid Lunds universitet,Genomiska analyser av urinblåscancer,Urology - urothelial cancer, Malmö,Lund University Research Groups,Urothelial Cancer Genomics(Swepub:lu)med-gsj
(författare)
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Kardos, JordanUniversity of North Carolina
(författare)
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Hoadley, Katherine A.University of North Carolina
(författare)
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Lerner, Seth P.Baylor College of Medicine
(författare)
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McConkey, David J.University of Texas
(författare)
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Choi, WoonyoungUniversity of Texas
(författare)
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Kim, William Y.University of North Carolina
(författare)
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Kiss, BernhardUniversity of Bern
(författare)
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Thalmann, George N.University of Bern
(författare)
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Todenhöfer, TilmanUniversity of British Columbia
(författare)
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Crabb, Simon J.University Hospital Southampton
(författare)
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North, ScottUniversity of Alberta
(författare)
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Zwarthoff, Ellen C.Erasmus University Medical Center
(författare)
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Boormans, Joost L.Erasmus University Medical Center
(författare)
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Wright, JonathanWashington University School of Medicine
(författare)
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Dall'Era, MarcUniversity of California, Davis
(författare)
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van der Heijden, Michiel S.Antoni Van Leeuwenhoek Hospital
(författare)
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Black, Peter C.University of British Columbia
(författare)
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University of BernGenomeDx Biosciences
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:European Urology: Elsevier BV72:4, s. 544-5540302-2838
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Seiler, Roland
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Ashab, Hussam Al ...
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Erho, Nicholas
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van Rhijn, Bas W ...
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Winters, Brian
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Douglas, James J
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visa fler...
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van Kessel, Kim ...
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Fransen van de P ...
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Sommerlad, Matth ...
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Wang, Natalie Q.
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Choeurng, Voleak
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Gibb, Ewan A.
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Palmer-Aronsten, ...
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Lam, Lucia L.
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Buerki, Christin ...
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Davicioni, Elai
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Sjödahl, Gottfri ...
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Kardos, Jordan
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Hoadley, Katheri ...
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Lerner, Seth P.
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McConkey, David ...
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Choi, Woonyoung
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Kim, William Y.
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Kiss, Bernhard
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Thalmann, George ...
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Todenhöfer, Tilm ...
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Crabb, Simon J.
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North, Scott
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Zwarthoff, Ellen ...
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Boormans, Joost ...
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Wright, Jonathan
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Dall'Era, Marc
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van der Heijden, ...
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Black, Peter C.
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