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

Lindskrog SV, Prip F, Lamy P, Taber A, Groeneveld CS, Birkenkamp-Demtröder K, Jensen JB, Strandgaard T, Nordentoft I, Christensen E, Sokac M, Birkbak NJ, Maretty L, Hermann GG, Petersen AC, Weyerer V, Grimm MO, Horstmann M, Sjödahl G, Höglund M, Steiniche T, Mogensen K, de Reyniès A, Nawroth R, Jordan B, Lin X, Dragicevic D, Ward DG, Goel A, Hurst CD, Raman JD, Warrick JI, Segersten U, Sikic D, van Kessel KE, Maurer T, Meeks JJ, DeGraff DJ, Bryan RT, Knowles MA, Simic T, Hartmann A, Zwarthoff EC, Malmström PU, Malats N, Real FX, Dyrskjøt L (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Book Volume: 12

Article Number: 2301

Journal Issue: 1

DOI: 10.1038/s41467-021-22465-w

Abstract

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.

Authors with CRIS profile

Involved external institutions

University of Belgrade / Универзитет у Београду Serbia (RS) Erasmus University Medical Center (MC) Netherlands (NL) Aarhus University Hospital / Aarhus Universitetshospital Denmark (DK) Carte d'Identité des Tumeurs (CIT Program) France (FR) Aarhus University Denmark (DK) University of Copenhagen Denmark (DK) Aalborg Universitetshospital Denmark (DK) Universitätsklinikum Jena Germany (DE) Lund University / Lunds universitet Sweden (SE) Klinikum rechts der Isar Germany (DE) Northwestern University United States (USA) (US) University of Birmingham United Kingdom (GB) University of Leeds United Kingdom (GB) Pennsylvania State University (Penn State) United States (USA) (US) Uppsala University Sweden (SE) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES)

How to cite

APA:

Lindskrog, S.V., Prip, F., Lamy, P., Taber, A., Groeneveld, C.S., Birkenkamp-Demtröder, K.,... Dyrskjøt, L. (2021). An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer. Nature Communications, 12(1). https://dx.doi.org/10.1038/s41467-021-22465-w

MLA:

Lindskrog, Sia Viborg, et al. "An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer." Nature Communications 12.1 (2021).

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