Researchers Discover New Epigenetic Biomarkers for Prostate Cancer

Cancer that occurs in the prostate is one of the most common cancers found in men globally. It is also clinically one of the most varied, with a subgroup of patients that advance more quickly to metastasis. Unfortunately, many diagnostic measures used today are not capable of predicting prostate cancer’s (PC) progression. Because epigenetic modifications are usually found early in tumor development, researchers have become more interested in studying these changes to find biomarkers for the disease.

In a recent study conducted at the Garvan Institute of Medical Research, a team of scientists has found new epigenetic evidence that can be used to predict more aggressive types of PC. Using DNA methylation profiling, the group identified a suite of candidate prognostic biomarkers. Their results were published in the journal, Clinical and Translational Medicine.

While PC can be deadly, most men diagnosed with the disease don’t die from it. Early screening measures, innovative therapies, and patient monitoring have extended survival rates. However, the prevalence of PC, especially in older males, and sometimes lack of symptoms contribute to PC’s ranking as the second leading cause of death in men.

As PC tends to be a slower moving cancer, the earlier the diagnosis, the higher the survival rate – which is why novel detection methods are needed. Knowing sooner whether or not a patient will suffer from advanced PC permits clinicians to proceed with aggressive treatments right away.

“There’s a need for men with prostate cancer to have more personalized treatments guided by the nature of their tumors, and they can’t get that without new biomarkers that can better predict the risk of developing the lethal form of the disease,” said Prof. Susan Clark principal researcher of the study and head of the epigenetics laboratory at Garvan.

The study involved using a 20-year-old bank of PC biopsies held at Garvan and St Vincent’s Hospital from 185 men who had their prostrate removed. The team analyzed their samples and tracked how many men survived and died from the disease over the years.

Using whole-genome bisulphite sequencing (WGBS) to examine all of the genetic material, the team comprehensively mapped and compared DNA methylation in the samples between patients. DNA methylation is a molecular change that turns genes “on or off” and is known to be preserved throughout all stages of cancer.

The WGBS results revealed cancer-specific methylation patterns with increasing levels of disease risk. More than 1000 regions showed methylation changes between non-lethal and lethal patient groups. Among those regions, the researchers further studied 18 genes and noticed that one, CACNA2D4, stood out as a primary biomarker.

The CACNA2D4 gene is involved with calcium channel regulation and is not well studied in cancer. According to first author, Dr. Rught Pidsley, “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,”

Overall, the team’s epigenetic analysis showed distinct differences between men with non-lethal and lethal PC disease. The biomarkers identified are expected to improve upon existing PC prognostic tools and hold promise for the development of more personalized cancer treatments.

“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 Prof. Lisa Horvath, the study’s clinical leader and a Garvan researcher and oncologist. “These epigenetic biomarkers have the potential to help us work out up front who has lethal prostate cancer and who doesn’t.”

While more research is needed to validate the study’s results, the team has made their epigenome sequencing data public so that more researchers can benefit and hopefully build upon their findings. They also plan on extending the study to determine if the biomarkers are also seen in blood samples.

Source: Ruth Pidsley, et al. Comprehensive methylome sequencing reveals prognostic epigenetic biomarkers for prostate cancer mortality. Clinical and Translational Medicine, September 30, 2022.

Reference: New epigenetic markers for prostate cancer discovered. Garvan Institute of Medical Research. October 3, 2022.