Molecular correlates of cisplatin-based chemotherapy response in muscle invasive bladder cancer by integrated multi-omics analysis
Top Cited Papers
Open Access
- 25 September 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 11 (1), 1-15
- https://doi.org/10.1038/s41467-020-18640-0
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
This publication has 60 references indexed in Scilit:
- Signatures of mutational processes in human cancerNature, 2013
- Genome-wide peripheral blood leukocyte DNA methylation microarrays identified a single association with inflammatory bowel diseasesInflammatory Bowel Diseases, 2012
- Association of BRCA1 and BRCA2 Mutations With Survival, Chemotherapy Sensitivity, and Gene Mutator Phenotype in Patients With Ovarian CancerJAMA, 2011
- Allele-specific copy number analysis of tumorsProceedings of the National Academy of Sciences, 2010
- ConsensusClusterPlus: a class discovery tool with confidence assessments and item trackingBioinformatics, 2010
- edgeR: a Bioconductor package for differential expression analysis of digital gene expression dataBioinformatics, 2009
- The Sequence Alignment/Map format and SAMtoolsBioinformatics, 2009
- New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)European Journal Of Cancer, 2009
- A role for neoadjuvant gemcitabine plus cisplatin in muscle‐invasive urothelial carcinoma of the bladderCancer, 2008
- Research electronic data capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics supportJournal of Biomedical Informatics, 2008