Iver Kristiansen Nordentoft

An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Sia Viborg Lindskrog
  • Frederik Prip
  • Philippe Lamy
  • ,
  • Ann Taber
  • ,
  • Clarice S. Groeneveld, Ligue Nationale Contre le Cancer, Institut Curie
  • ,
  • Karin Birkenkamp-Demtröder
  • Jørgen Bjerggaard Jensen
  • Trine Strandgaard
  • Iver Nordentoft
  • Emil Christensen
  • Mateo Sokac
  • Nicolai J. Birkbak
  • Lasse Maretty
  • Gregers G. Hermann, University of Copenhagen
  • ,
  • Astrid C. Petersen, Aalborg Universitetshospital
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  • Veronika Weyerer, Friedrich-Alexander University Erlangen-Nürnberg
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  • Marc Oliver Grimm, Jena University Hospital
  • ,
  • Marcus Horstmann, Friedrich Schiller University Jena, Malteser Hospital St. Josephshospital
  • ,
  • Gottfrid Sjödahl, Skåne University Hospital Malmö
  • ,
  • Mattias Höglund, Lund University
  • ,
  • Torben Steiniche
  • Karin Mogensen, University of Copenhagen
  • ,
  • Aurélien de Reyniès, Ligue Nationale Contre le Cancer
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  • Roman Nawroth, Technical University of Munich
  • ,
  • Brian Jordan, Northwestern University
  • ,
  • Xiaoqi Lin, Northwestern University
  • ,
  • Dejan Dragicevic, University of Belgrade
  • ,
  • Douglas G. Ward, University of Birmingham
  • ,
  • Anshita Goel, University of Birmingham
  • ,
  • Carolyn D. Hurst, University of Leeds
  • ,
  • Jay D. Raman, Pennsylvania State University
  • ,
  • Joshua I. Warrick, Pennsylvania State University
  • ,
  • Ulrika Segersten, Uppsala University
  • ,
  • Danijel Sikic, Friedrich-Alexander University Erlangen-Nürnberg
  • ,
  • Kim E.M. van Kessel, Erasmus University Rotterdam
  • ,
  • Tobias Maurer, Technical University of Munich, University of Hamburg
  • ,
  • Joshua J. Meeks, Northwestern University
  • ,
  • David J. DeGraff, Pennsylvania State University
  • ,
  • Richard T. Bryan, University of Birmingham
  • ,
  • Margaret A. Knowles, University of Leeds
  • ,
  • Tatjana Simic, University of Belgrade
  • ,
  • Arndt Hartmann, Friedrich-Alexander University Erlangen-Nürnberg
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  • Ellen C. Zwarthoff, Erasmus University Rotterdam
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  • Per Uno Malmström, Uppsala University
  • ,
  • Núria Malats, Spanish National Cancer Research Centre (CNIO)
  • ,
  • Francisco X. Real, Instituto de Salud Carlos III, Pompeu Fabra University
  • ,
  • Lars Dyrskjøt

The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed with NMIBC (n = 834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters. High chromosomal instability, p53-pathway disruption and APOBEC-related mutations are significantly associated with transcriptomic class 2a and poor outcome. RNA-derived immune cell infiltration is associated with chromosomally unstable tumors and enriched in class 2b. Spatial proteomics analysis confirms the higher infiltration of class 2b tumors and demonstrates an association between higher immune cell infiltration and lower recurrence rates. Finally, the independent prognostic value of the transcriptomic classes is documented in 1228 validation samples using a single sample classification tool. The classifier provides a framework for biomarker discovery and for optimizing treatment and surveillance in next-generation clinical trials.

Original languageEnglish
Article number2301
JournalNature Communications
Volume12
Issue1
Number of pages18
ISSN2041-1723
DOIs
Publication statusPublished - 2021

Bibliographical note

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© 2021, The Author(s).

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Copyright 2021 Elsevier B.V., All rights reserved.

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