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Molecular correlates of cisplatin-based chemotherapy response in muscle invasive bladder cancer by integrated multi-omics analysis.
- Source :
-
Nature communications [Nat Commun] 2020 Sep 25; Vol. 11 (1), pp. 4858. Date of Electronic Publication: 2020 Sep 25. - Publication Year :
- 2020
-
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.
- Subjects :
- BRCA2 Protein genetics
BRCA2 Protein metabolism
Biomarkers, Tumor
Chemotherapy, Adjuvant
Cisplatin therapeutic use
DNA Methylation
Drug Therapy
Genomic Instability
Humans
Mutation
Neoadjuvant Therapy
Programmed Cell Death 1 Receptor genetics
Programmed Cell Death 1 Receptor metabolism
Transcriptome
Urinary Bladder Neoplasms pathology
Cisplatin pharmacology
Gene Expression Regulation, Neoplastic drug effects
Urinary Bladder Neoplasms drug therapy
Urinary Bladder Neoplasms genetics
Urinary Bladder Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 32978382
- Full Text :
- https://doi.org/10.1038/s41467-020-18640-0