BERKELEY, CA (UroToday.com) - Due to increased screening, more men are discovering that they have developed prostate cancer, but may not appreciate that most cancers are indolent. Thus, the major dilemma accompanying a diagnosis of prostate cancer is whether the patient can reasonably expect to benefit from treatment. While 1-in-6 men are likely to be diagnosed with prostate cancer, only 1-in-36 will ultimately die from the disease, reflecting a 5-year survival rate of nearly 100%. Available treatments can be harsh and substantially undermine a patient’s quality of life due to common, severe side effects such as incontinence and impotence. However, choosing active surveillance may allow some inapparent aggressive cancers to progress. In addition, the initial avoidance of presumptive, effective treatment may cause anxiety and ultimately drive patients to demand treatments which they did not need. Therefore, development of biomarkers to accurately separate aggressive from indolent cancers at the point of initial diagnosis are urgently needed.
DNA methylation is an important mechanism coordinating expression of genes during normal development. Aberrant DNA methylation causes loss of control of gene expression, which is a hallmark of carcinogenesis. Decades of research have shown that alterations of methylation of different genes, in most cancer types, have valuable diagnostic and prognostic potential. Another advantage is that methylation is measurable by a wide range of molecular approaches, some of which are suitable for the development of simple and inexpensive assays.
The aim of the current investigation was to assess the potential biomarker value of changes in methylation of the HSPB1 gene. Changes in the expression of the corresponding heat shock protein Hsp27 were previously shown to predict aggressive disease with poor clinical outcome. We found that changes in methylation of HSPB1 were significantly associated with death from prostate cancer and were particularly informative for predicting aggressive cancers in men with low Gleason score (< 7), a group which is normally regarded as of low risk. Using the same cohort, we subsequently measured methylation of an additional 12 genes (paper in preparation). In a multivariate analysis, HSPB1 and its interaction with Gleason score remained a part of the best prognostic model, further underlining its importance in prostate cancer. Interestingly, when we investigated an additional, larger set of patients, the prognostic potential of HSPB1 methylation was confirmed (paper in preparation). Finally, using the combined data from the entire cohort of more than 650 men with almost 200 prostate cancer-specific deaths, HSPB1 methylation remained a highly significant independent predictor of prostate cancer-specific death.
In conclusion, our data demonstrate that abnormal DNA methylation of HSPB1 carries important information on the risk of death in the subsequent 15 years after diagnosis and is especially informative in men who may believe that they are at low risk. We are proceeding to external validations and exploring the options for a future routine clinical test.
Written by:
N. Vasiljević, A. S. Ahmad, and A. T. Lorincz as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK
Association between DNA methylation of HSPB1 and death in low Gleason score prostate cancer - Abstract
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