Mark O. Kitchen
HumanMethylation450K array–identified biomarkers predict tumour recurrence/progression at initial diagnosis of high-risk non-muscle Invasive bladder cancer
Kitchen, Mark O.; Bryan, Richard T.; Emes, Richard D.; Luscombe, Christopher J.; Cheng, K.K.; Zeegers, Maurice P.; James, Nicholas D.; Gommersall, Lyndon M.; Fryer, Anthony A.
Authors
Richard T. Bryan
Richard D. Emes
Christopher J. Luscombe
K.K. Cheng
Maurice P. Zeegers
Nicholas D. James
Lyndon M. Gommersall
Anthony A. Fryer
Abstract
Background: High-risk non-muscle invasive bladder cancer (HR-NMIBC) is a clinically unpredictable disease. Despite clinical risk estimation tools, many patients are undertreated with intra-vesical therapies alone, whereas others may be over-treated with early radical surgery.
Molecular biomarkers, particularly DNA methylation, have been reported as predictive of tumour/patient outcomes in numerous solid organ and haematologic malignancies; however, there are few reports in HR-NMIBC and none using genome-wide array assessment. We therefore sought to identify novel DNA methylation markers of HR-NMIBC clinical outcomes that might predict tumour behaviour at initial diagnosis and help guide patient management.
Patients and methods: A total of 21 primary initial diagnosis HR-NMIBC tumours were analysed by Illumina HumanMethylation450 BeadChip arrays and subsequently bisulphite Pyrosequencing. In all, 7 had not recurred at 1 year after resection and 14 had recurred and/or progressed despite intra-vesical BCG. A further independent cohort of 32 HR-NMIBC tumours (17 no recurrence and 15 recurrence and/ or progression despite BCG) were also assessed by bisulphite Pyrosequencing.
Results: Array analyses identified 206 CpG loci that segregated non-recurrent HR-NMIBC tumours from clinically more aggressive recurrence/progression tumours. Hypermethylation of CpG cg11850659 and hypomethylation of CpG cg01149192 in combination predicted HRNMIBC recurrence and/or progression within 1 year of diagnosis with 83% sensitivity, 79% specificity, and 83% positive and 79% negative predictive values.
Conclusions: This is the first genome-wide DNA methylation analysis of a unique HR-NMIBC tumour cohort encompassing known 1-year clinical outcomes. Our analyses identified potential novel epigenetic markers that could help guide individual patient management in this clinically unpredictable disease
Journal Article Type | Article |
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Acceptance Date | Nov 15, 2017 |
Online Publication Date | Jan 8, 2018 |
Deposit Date | Apr 20, 2018 |
Publicly Available Date | Apr 20, 2018 |
Journal | Biomarkers in Cancer |
Electronic ISSN | 1179-299X |
Publisher | Libertas Academica |
Peer Reviewed | Peer Reviewed |
Keywords | high-risk non-muscle invasive bladder cancer, epigenetics, methylation, HumanMethylation450 BeadChip array, prognostic biomarker |
Public URL | https://nottingham-repository.worktribe.com/output/903740 |
Publisher URL | http://journals.sagepub.com/doi/10.1177/1179299X17751920 |
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Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc/4.0
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