Molecular correlates of cisplatin-based chemotherapy response in muscle invasive bladder cancer by integrated multi-omics analysis

Ann Taber, Emil Christensen, Philippe Lamy, Iver Nordentoft, Frederik Prip, Sia Viborg Lindskrog, Karin Birkenkamp-Demtröder, Trine Line Hauge Okholm, Michael Knudsen, Jakob Skou Pedersen, Torben Steiniche, Mads Agerbæk, Jørgen Bjerggaard Jensen and Lars Dyrskjøt ()
Additional contact information
Ann Taber: Aarhus University Hospital
Emil Christensen: Aarhus University Hospital
Philippe Lamy: Aarhus University Hospital
Iver Nordentoft: Aarhus University Hospital
Frederik Prip: Aarhus University Hospital
Sia Viborg Lindskrog: Aarhus University Hospital
Karin Birkenkamp-Demtröder: Aarhus University Hospital
Trine Line Hauge Okholm: Aarhus University Hospital
Michael Knudsen: Aarhus University Hospital
Jakob Skou Pedersen: Aarhus University Hospital
Torben Steiniche: Aarhus University Hospital
Mads Agerbæk: Aarhus University Hospital
Jørgen Bjerggaard Jensen: Aarhus University
Lars Dyrskjøt: Aarhus University Hospital

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract Overtreatment with cisplatin-based chemotherapy is a major issue in the management of muscle-invasive bladder cancer (MIBC), and currently none of the reported biomarkers for predicting response have been implemented in the clinic. Here we perform a comprehensive multi-omics analysis (genomics, transcriptomics, epigenomics and proteomics) of 300 MIBC patients treated with chemotherapy (neoadjuvant or first-line) to identify molecular changes associated with treatment response. DNA-based associations with response converge on genomic instability driven by a high number of chromosomal alterations, indels, signature 5 mutations and/or BRCA2 mutations. Expression data identifies the basal/squamous gene expression subtype to be associated with poor response. Immune cell infiltration and high PD-1 protein expression are associated with treatment response. Through integration of genomic and transcriptomic data, we demonstrate patient stratification to groups of low and high likelihood of cisplatin-based response. This could pave the way for future patient selection following validation in prospective clinical trials.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-18640-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18640-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-18640-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().