Researchers Discover New Epigenetic Markers for Prostate Cancer

Prostate cancer is the second most common cancer diagnosed in men worldwide, with about half acquiring metastatic cancer after initial diagnosis. To learn more about this aggressive cancer, researchers at the Garvan Institute of Medical Research have uncovered new epigenetic biomarkers that can be used to develop better treatment plans.

“There’s a need for men with prostate cancer to have more personalised treatments guided by the nature of their tumours, and they can’t get that without new biomarkers that can better predict the risk of developing the lethal form the disease,” says lead author Susan Clark, Head of the Epigenetic Research Lab at Garvan.

The study, which was published in the journal Clinical and Translational Medicine, comprises one of the most long-term molecular studies of prostate cancer progression. This cancer’s slow progression has traditionally made studying its mechanisms difficult, but the Garvan and St Vincent Hospital’s bank biopsies made it easier for researchers to check multiple samples from different time points. The bank of biopsies has been maintained for the last 20 years, allowing researchers to analyze samples from 185 men with their prostate removed due to a cancer diagnosis between 1990-2000. Then, the team tracked the number of men who survived and died from the disease.

By assessing their genomes, the team was able to identify 1420 regions specific to prostate cancer where they observed epigenetic changes, specifically via DNA methylation. Of those regions, 18 were studied more thoroughly, with one standing out as a key biomarker – the CACNA2D4 gene involved with calcium channel regulation.

“There’s very little known about this gene and it’s not typically profiled, so we really need to understand how the methylation process may suppress the gene’s activity,” says first author Dr. Ruth Pidsley. The team’s comprehensive epigenome sequencing is now available online for other scientists to further prostate cancer research. For future work, the team wants to see if these biomarkers can be effectively detected in blood samples.

Not only did these current results show differences in the individuals with lethal and non-lethal forms of prostate cancer, but the biomarkers can also improve existing clinical tools for prognosis and treatment. “What you really want to know on the day a patient is diagnosed, is who has the potential for lethal prostate cancer and who doesn’t, because it will change the way you treat the cancer,” says Garvan researcher and oncologist Professor Lisa Horvath, who was the clinical lead on the study. “These epigenetic biomarkers have the potential to help us work out up front who has lethal prostate cancer and who doesn’t.”