DNA methylation gene-based models indicating independent poor outcome in prostate cancer

BMC Cancer

Nataša Vasiljević⁴  Amar S Ahmad⁴  Mangesh A Thorat⁴  Gabrielle Fisher⁴  Daniel M Berney³  Henrik Møller¹  Christopher S Foster²  Jack Cuzick⁴  Attila T Lorincz⁴ 

[1] King’s College London, Cancer Epidemiology and Population Health, London SE1 9RT, UK

[2] HCA International Pathology Laboratories, 2-22 Capper Street, London WC1E 6JA, UK

[3] Molecular Oncology Centre, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK

[4] Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine, Queen Mary University of London, London EC1M 6BQ, UK

关键词: Pyrosequencing;    Watchful waiting;    Progression biomarkers;    Prostate cancer;    DNA methylation;   

Others  :  1121103
DOI  :  10.1186/1471-2407-14-655

 received in 2014-03-16, accepted in 2014-08-30,  发布年份 2014

【 摘 要 】

Background

Prostate cancer has a variable clinical behaviour with frequently unpredictable outcome. DNA methylation plays an important role in determining the biology of cancer but prognostic information is scanty. We assessed the potential of gene-specific DNA methylation changes to predict death from prostate cancer in a cohort of untreated men in the UK.

Methods

This was a population-based study in which cases were identified from six cancer registries in Great Britain. DNA was extracted from formalin-fixed paraffin wax-embedded transurethral prostate resection tissues collected during 1990-96 from men with clinically-localised cancer who chose not to be treated for at least 6 months following diagnosis. The primary end point was death from prostate cancer. Outcomes were determined through medical records and cancer registry records. Pyrosequencing was used to quantify methylation in 13 candidate genes with established or suggested roles in cancer. Univariate and multivariate Cox models were used to identify possible predictors for prostate cancer-related death.

Results

Of 367 men, 99 died from prostate cancer during a median of 9.5 years follow-up (max = 20). Univariately, 12 genes were significantly associated with prostate cancer mortality, hazard ratios ranged between 1.09 and 1.28 per decile increase in methylation. Stepwise Cox regression modelling suggested that the methylation of genes HSPB1, CCND2 and DPYS contributed objective prognostic information to Gleason score and PSA with respect to cancer-related death during follow-up (p = 0.006).

Conclusion

Methylation of 13 genes was analysed in 367 men with localised prostate cancer who were conservatively treated and stratified with respect to death from prostate cancer and those who survived or died of other causes. Of the 13 genes analysed, differential methylation of HSPB1, CCND2 and DPYS provided independent prognostic information. Assessment of gene-methylation may provide independent objective information that can be used to segregate prostate cancers at diagnosis into predicted behavioural groups.

【 授权许可】

   
2014 Vasiljevic et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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