HumanMethylation450K Array–Identified Biomarkers Predict Tumour Recurrence/Progression at Initial Diagnosis of High-risk Non-muscle Invasive Bladder Cancer. Issue 10 (6th January 2018)

• Record Type: Journal Article
• Authors: Kitchen, Mark O; Bryan, Richard T; Emes, Richard D; Luscombe, Christopher J; Cheng, KK; Zeegers, Maurice P; James, Nicholas D; Gommersall, Lyndon M; Fryer, Anthony A
• Is Part Of: Biomarkers in cancer. Volume 2018:Issue 10(2018)
• Publication Date: 2018-01-06
• Subjects: high-risk non-muscle invasive bladder cancer -- epigenetics -- methylation -- HumanMethylation450 BeadChip array -- prognostic biomarker; Tumor markers -- Periodicals; Cancer -- Periodicals; Biochemical markers -- Periodicals; 616.99405
• DOI: 10.1177/1179299X17751920
• Languages: English
• ISSNs: 1179-299X

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 HR-NMIBC 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.