New epigenetic markers for aggressive prostate cancer

Prostate cancer is the second most common male cancer
worldwide.
After diagnosis, about 50% of men will develop metastatic cancer
in their lifetime.
Typically, metastases take 15 years or more to occur, but a small percentage of men develop fatal metastases
earlier after diagnosis.
By identifying patients who may develop into this type of prostate cancer at an early stage, clinicians can start more aggressive treatment
earlier.
Scientists at the Gavin Institute of Medicine have discovered new epigenetic biomarkers that can predict a more aggressive form of
prostate cancer.

These biomarkers can be used in conjunction with traditional clinical tools to predict whether men will develop a more metastatic and fatal disease and can help clinicians develop better treatment options
.

Professor Susan Clark, head of the Epigenetic Research Laboratory and principal investigator of the study, said: "Prostate cancer patients need more personalized treatment based on the nature of their tumor, and without new biomarkers, they cannot access this treatment because these biomarkers can better predict the risk of
developing this deadly disease.
"

This study, published in Clinical and Translational Medicine, is one of
the longest-running and comprehensive molecular studies of prostate cancer progression.
The slow progression of the disease makes it difficult
to study biology.

Garvan and St Vincent Hospital kept a 20-year-old biopsy library, allowing researchers to analyze samples of 185 men who had their prostate removed from a diagnosis of prostate cancer in the 1990s and early 2000s
.
The team then tracked the number of men who survived and those who died from the disease, some of whom died of the
disease 15 years later.

The researchers looked at their genomes and identified 1420 prostate cancer-specific regions where they could see epigenetic changes — markers on DNA, known as DNA methylation
.
The methylation process can increase or decrease the activity
of genes without altering the DNA sequence as a mutation.

In these regions, 18 genes were further studied, and one of the prominent biomarkers was the CACNA2D4 gene, which is associated
with calcium channel regulation.

Dr.
Ruth Pidsley, lead author of the study, said: "We know very little about this gene and there is no typical description, so we really need to understand how the methylation process inhibits
gene activity.
"

The team has made comprehensive epigenome sequencing data available to other researchers for further prostate cancer research
.

The results of epigenomic analysis not only show differences between patients with fatal and non-fatal prostate cancer, but biomarkers also improve existing clinical tools
for prognosis.

The new findings offer hope
for more personalized cancer treatment.

Oncologist and researcher Professor Lisa Horvath, who led the clinical lead in the study, said: "The day a patient is diagnosed with fatal prostate cancer, what you really want to know is who is at risk of developing fatal prostate cancer and who is not, because that will change the way
you treat cancer.
" These epigenetic biomarkers have the potential to help us predetermine who has fatal prostate cancer and who doesn't
.
”

The next step is to expand the scope of the study and determine whether biomarkers
can be detected in blood samples in the first place.

 Comprehensive methylome sequencing reveals prognostic epigenetic biomarkers for prostate cancer mortality