Molecular correlates of cisplatin-based chemotherapy response in muscle invasive bladder cancer by integrated multi-omics analysis
| Autor: | Jørgen Bjerggaard Jensen, Frederik Prip, Emil Christensen, Michael Knudsen, Philippe Lamy, Trine Line Hauge Okholm, Ann Taber, Torben Steiniche, Jakob Skou Pedersen, Sia Viborg Lindskrog, Karin Birkenkamp-Demtröder, Iver Nordentoft, Lars Dyrskjøt, Mads Agerbæk |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Genome instability Oncology Cisplatin/pharmacology Molecular biology CYSTECTOMY medicine.medical_treatment Programmed Cell Death 1 Receptor General Physics and Astronomy Proteomics Transcriptome NEOADJUVANT CHEMOTHERAPY 0302 clinical medicine lcsh:Science Neoadjuvant therapy Cancer Epigenomics Multidisciplinary Molecular medicine Urinary Bladder Neoplasms/drug therapy GEMCITABINE PLUS CISPLATIN ASSOCIATION CLONAL EVOLUTION BRCA2 Protein/genetics Neoadjuvant Therapy Gene Expression Regulation Neoplastic Chemotherapy Adjuvant 030220 oncology & carcinogenesis DNA methylation Allelic Imbalance SURVIVAL SENSITIVITY medicine.drug medicine.medical_specialty CARCINOMA Urology Science SOMATIC ERCC2 MUTATIONS Genomics Context (language use) Article General Biochemistry Genetics and Molecular Biology Genomic Instability 03 medical and health sciences Medical research Drug Therapy Programmed Cell Death 1 Receptor/genetics Internal medicine medicine Biomarkers Tumor Humans SIGNATURES Cisplatin BRCA2 Protein Bladder cancer business.industry General Chemistry DNA Methylation medicine.disease 030104 developmental biology Urinary Bladder Neoplasms Gene Expression Regulation Neoplastic/drug effects Mutation lcsh:Q business Biomarkers |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-15 (2020) Taber, A, Christensen, E, Lamy, P, Nordentoft, I, Prip, F, Lindskrog, S V, Birkenkamp-Demtröder, K, Okholm, T L H, Knudsen, M, Pedersen, J S, Steiniche, T, Agerbæk, M, Jensen, J B & Dyrskjøt, L 2020, ' Molecular correlates of cisplatin-based chemotherapy response in muscle invasive bladder cancer by integrated multi-omics analysis ', Nature Communications, vol. 11, no. 1, 4858 . https://doi.org/10.1038/s41467-020-18640-0 Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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