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

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Standard

Molecular correlates of cisplatin-based chemotherapy response in muscle invasive bladder cancer by integrated multi-omics analysis. / Taber, Ann; Christensen, Emil; Lamy, Philippe et al.

I: Nature Communications, Bind 11, Nr. 1, 4858, 09.2020.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

APA

CBE

MLA

Vancouver

Author

Bibtex

@article{ab751b93b681463db3b0df4c8010b41f,
title = "Molecular correlates of cisplatin-based chemotherapy response in muscle invasive bladder cancer by integrated multi-omics analysis",
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.",
keywords = "ASSOCIATION, CARCINOMA, CLONAL EVOLUTION, CYSTECTOMY, GEMCITABINE PLUS CISPLATIN, NEOADJUVANT CHEMOTHERAPY, SENSITIVITY, SIGNATURES, SOMATIC ERCC2 MUTATIONS, SURVIVAL, Genomic Instability, Humans, Drug Therapy, Transcriptome, Gene Expression Regulation, Neoplastic/drug effects, Biomarkers, Tumor, Urinary Bladder Neoplasms/drug therapy, Programmed Cell Death 1 Receptor/genetics, BRCA2 Protein/genetics, Cisplatin/pharmacology, DNA Methylation, Neoadjuvant Therapy, Chemotherapy, Adjuvant, Mutation",
author = "Ann Taber and Emil Christensen and Philippe Lamy and Iver Nordentoft and Frederik Prip and Lindskrog, {Sia Viborg} and Karin Birkenkamp-Demtr{\"o}der and Okholm, {Trine Line Hauge} and Michael Knudsen and Pedersen, {Jakob Skou} and Torben Steiniche and Mads Agerb{\ae}k and Jensen, {J{\o}rgen Bjerggaard} and Lars Dyrskj{\o}t",
year = "2020",
month = sep,
doi = "10.1038/s41467-020-18640-0",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Molecular correlates of cisplatin-based chemotherapy response in muscle invasive bladder cancer by integrated multi-omics analysis

AU - Taber, Ann

AU - Christensen, Emil

AU - Lamy, Philippe

AU - Nordentoft, Iver

AU - Prip, Frederik

AU - Lindskrog, Sia Viborg

AU - Birkenkamp-Demtröder, Karin

AU - Okholm, Trine Line Hauge

AU - Knudsen, Michael

AU - Pedersen, Jakob Skou

AU - Steiniche, Torben

AU - Agerbæk, Mads

AU - Jensen, Jørgen Bjerggaard

AU - Dyrskjøt, Lars

PY - 2020/9

Y1 - 2020/9

N2 - 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.

AB - 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.

KW - ASSOCIATION

KW - CARCINOMA

KW - CLONAL EVOLUTION

KW - CYSTECTOMY

KW - GEMCITABINE PLUS CISPLATIN

KW - NEOADJUVANT CHEMOTHERAPY

KW - SENSITIVITY

KW - SIGNATURES

KW - SOMATIC ERCC2 MUTATIONS

KW - SURVIVAL

KW - Genomic Instability

KW - Humans

KW - Drug Therapy

KW - Transcriptome

KW - Gene Expression Regulation, Neoplastic/drug effects

KW - Biomarkers, Tumor

KW - Urinary Bladder Neoplasms/drug therapy

KW - Programmed Cell Death 1 Receptor/genetics

KW - BRCA2 Protein/genetics

KW - Cisplatin/pharmacology

KW - DNA Methylation

KW - Neoadjuvant Therapy

KW - Chemotherapy, Adjuvant

KW - Mutation

UR - http://www.scopus.com/inward/record.url?scp=85091566862&partnerID=8YFLogxK

U2 - 10.1038/s41467-020-18640-0

DO - 10.1038/s41467-020-18640-0

M3 - Journal article

C2 - 32978382

AN - SCOPUS:85091566862

VL - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 4858

ER -