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

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• dc.contributor.author Lindskrog, Sia Viborg
• dc.contributor.author Real, Francisco X.
• dc.contributor.author Dyrskjøt, Lars
• dc.date.accessioned 2021-05-10T07:38:48Z
• dc.date.available 2021-05-10T07:38:48Z
• dc.date.issued 2021
• dc.description.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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Lindskrog SV, Prip F, Lamy P, Taber A, Groeneveld CS, Birkenkamp-Demtröder K et al. An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer. Nat Commun. 2021;12(1):2301. DOI: 10.1038/s41467-021-22465-w
• dc.identifier.doi http://dx.doi.org/10.1038/s41467-021-22465-w
• dc.identifier.issn 2041-1723
• dc.identifier.uri http://hdl.handle.net/10230/47361
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Nat Commun. 2021;12(1):2301
• dc.rights © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Bladder cancer
• dc.subject.keyword Cancer genomics
• dc.subject.keyword Cancer microenvironment
• dc.subject.keyword Computational biology and bioinformatics
• dc.title An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion