Genetic Signature Predicts Prostate Cancer Prognosis

Genetic Signature Predicts Prostate Cancer Prognosis

A genetic signature made up of 16 gene variants can predict if men with prostate cancer will respond to therapy and how likely their cancer is to spread.

The researchers, based at Columbia University Irving Medical Center in New York, hope that testing men with prostate cancer for this signature could help to personalize therapy better and in addition to identifying those that are at most need of treatment, could also help others to avoid unnecessary treatments or procedures.

“If we could know in advance which patients will develop metastases, we could start treatments earlier and treat the cancer more aggressively,” says Cory Abate-Shen, Ph.D., a professor at Columbia University and senior researcher on the study

Similar to breast cancer, many cases of prostate cancer are now successfully treated. The majority of cases remain in the prostate and can be treated by surgery or radiotherapy with 5-year survival rates of almost 100%.

However, despite this, a few cases do spread beyond the prostate and once this happens 5-year survival drops to around 30%. As it is a common cancer, 1 man in 9 will develop it in their lifetime, and around 33,330 men in the US die from this cancer every year.

It can be difficult to assess which cases of prostate cancer are likely to progress and so new methods of predicting this are sorely needed.

“The problem is that with existing tests, it’s hard to know which cancers are which,” says Juan Arriaga, Ph.D, an associate research scientist at Columbia University Vagelos College of Physicians and Surgeons, and lead author on the study describing the work, which was published in the journal Nature Cancer.

“We miss a lot of aggressive cancers that should have been treated earlier, and we over treat some slow-growing cancers that probably would not have spread.”

To address this issue, the team first looked for genetic predictors of metastases and tumor progression in a mouse model of the cancer. The most common area that prostate cancer spreads to is bone and the researchers looked closely at gene variants associated with this type of progression in mice and found that the molecular profile was similar to that in humans.

Notably, the researchers found that variation in the MYC and RAS genes can activate metastases in prostate cancer, as well as variation in 14 other genes. With this information, the team created a predictive signature they called META-16 that was able to accurately predict metastases in human prostate cancer patients when tested on samples taken from those with and without metastases. The signature was also able to predict the response that patients had to anti-androgen therapy, a common treatment for prostate cancer.

“The genes in our signature are not only correlated with metastasis, they appear to be driving metastasis,” Arriaga says. “That means that if that we can suppress the activity of those genes, we might be able prevent the cancer from spreading or at least improve outcomes.”

This research is still at an early stage, but the team hopes to test the META-16 signature in a bigger cohort in a clinical trial.