For many men, nothing can kick off a mid-life crisis quicker than a prostate exam. Middle-aged guys in sports cars everywhere dread reminders from their urologist for prostate checkups. Don’t even get us started on PSA’s infamous counterpart, the digital rectal exam.
The prostate surface antigen (PSA) test was launched back in 1985 by Hybritech, the common source of most old timers in the San Diego biotech community. As the first monoclonal-based antibody test for prostate cancer, the PSA test quickly became a physician’s standard for diagnosing and monitoring prostate cancer in patients.
Since then, despite being the most widely adopted screening test for prostate cancer, the PSA test has come under fire. When is the most appropriate time for screening, for how long, and the risk/benefits equation have been debated at urology conferences worldwide for some time now.
Last week, two groups published preliminary data in the New England Journal of Medicine, that poured more fuel on the prostate debate (Check out the New York Times commentary if you prefer a lighter version), indicating that the resulting over-diagnoses and treatment from early prostate screening might offset potential mortality from the cancer. Regardless of your thoughts on PSA, it’s hard to argue that there might be a better alternative brewing in the research labs out there.
DNA Methylation Biomarkers in Prostate Cancer
Thankfully, many research groups, like the team from the University of Toronto and Mount Sinai Hospital in Canada who published in PLoS One last week, are working on more telling screening solutions for the future that involve epigenetic biomarkers.
The Canadian team published data from recent studies to identify potential diagnostic and prognostic biomarkers of prostate cancer. The group set out to identify novel regions of aberrant DNA methylation, a hallmark of cancer thought to arise early in tumorigenesis, making it a very promising candidate for effective screening.
Using CpG Island microarrays from Agilent, they performed genome-wide DNA methylation analyses, and identified many interesting methylated genes in prostate cancer as a whole, as well as several genes that were differentially methylated in high and low grade prostate cancer cell lines, PP4 and PP3. The team noticed that many CpG islands were both quantitatively more methylated, but also methylated at an increased frequency in PP4 tumors than those in PP3 grade samples, potentially corresponding to an increase in methylation of these genes as the tumor progresses to a higher stage.
They further validated and confirmed their results with bisulfite-based mass spectrometry and qPCR, then proceeded to take a closer look at HOXD3 and BMP7 because of the statistically significant array results, relevant biological function and known involvement in prostate cancer.
Both genes were demonstrated to be hypermethylated in prostate cancer, down regulated by hypermethylated promoters, and correlated with high-grade tumor development. The authors concluded that HOXD3, in particular, is a good candidate for a prostate cancer biomarker as it may be used as both a diagnostic tool, as well as a prognostic indicator of tumor grade.
Get the full details at PLoS ONE March 2009 or if you’re ready to take the dive into DNA methylation biomarkers, check out Agilent’s Open Genomics website for more on the tools used in this work.