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Molecular correlates of cisplatin-based chemotherapy response in muscle invasive bladder cancer by integrated multi-omics analysis
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Molecular correlates of cisplatin-based chemotherapy response in muscle invasive bladder cancer by integrated multi-omics analysis
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Journal Article
Molecular correlates of cisplatin-based chemotherapy response in muscle invasive bladder cancer by integrated multi-omics analysis
2020
Overview
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.
There are currently only a few biomarkers to predict the response of muscle invasive bladder cancer to therapy. Here, the authors analyse 300 tumors using exome and RNA sequencing and find that tumors with a high degree of genomic instability and a non-basal/squamous gene expression subtype are most likely to respond to treatment.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14
/ 14/32
/ 38
/ 42
/ 45/23
/ 45/91
/ 631/337
/ 631/67
/ 692/308
/ 692/4017
/ 692/53
/ Bladder
/ Cancer
/ DNA
/ Gene Expression Regulation, Neoplastic - drug effects
/ Genomics
/ Humanities and Social Sciences
/ Humans
/ Muscles
/ Mutation
/ Patients
/ Programmed Cell Death 1 Receptor - genetics
/ Programmed Cell Death 1 Receptor - metabolism
/ Science
/ Tumors
/ Urinary Bladder Neoplasms - drug therapy
/ Urinary Bladder Neoplasms - genetics
