HumanMethylation450K Array–Identified Biomarkers Predict Tumour Recurrence/Progression at Initial Diagnosis of High-risk Non-muscle Invasive Bladder Cancer
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Le résumé fourni par la source
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.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- HumanMethylation450K Array–Identified Biomarkers Predict Tumour Recurrence/Progression at Initial Diagnosis of High-risk Non-muscle Invasive Bladder Cancer
- Date Crossref
- 01/01/2018
- Éditeur
- SAGE Publications
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University Hospitals of North Midlands NHS Trust Urology Department pays non établi dans la noticeÉtablissement de santé
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Keele University Institute for Science and Technology in Medicine pays non établi dans la noticeUniversité ou école supérieure
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University of Birmingham Institute of Cancer and Genomic Sciences pays non établi dans la noticeUniversité ou école supérieure
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University of Nottingham Advanced Data Analysis Centre pays non établi dans la noticeUniversité ou école supérieure
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Maastricht University Medical Centre CAPHRI School for Public Health and Primary Care pays non établi dans la noticeOrganisme public
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Maastricht University pays non établi dans la noticeUniversité ou école supérieure
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Care and Public Health Research Institute pays non établi dans la noticeStructure de recherche
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University of Warwick Cancer Research Centre pays non établi dans la noticeUniversité ou école supérieure
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NUTRIM School of Nutrition and Translational Research in Metabolism pays non établi dans la noticeUniversité ou école supérieure
Urology Department — University Hospitals of North Midlands NHS Trust, Institute for Science and Technology in Medicine — Keele University et Institute of Cancer and Genomic Sciences — University of Birmingham, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.