Genetic Signature Could Predict Prostate Cancer Metastasis

Investigators have identified a gene signature that appears to predict whether prostate cancer is likely to spread and whether it will be susceptible to a common therapy for advanced disease.

The findings, published in the journal Nature Cancer, could prove to be a major advancement in the care of prostate cancer and help clear up a significant area of uncertainty in patient management.

In the United States, about 33,000 men die from prostate cancer each year. Overall, the cancer has a high survival rate; 99% percent of patients are alive 5 years after diagnosis. In most cases, the disease can be managed either with active surveillance or local therapy. However, in a minority of cases, the cancer spreads, most often to the bones. Once it spreads, the disease is considered incurable with a 5-year survival rate of just 30%.

Lead author Juan M. Arriaga, PhD, of Columbia University’s Vagelos College of Physicians and Surgeons, said existing tests do not allow physicians a reliable prediction of whether a patient’s cancer will spread.

“We miss a lot of aggressive cancers that should have been treated earlier,” he said, in a press release, “and we overtreat some slow-growing cancers that probably would not have spread.”

Arriaga and colleagues decided to investigate whether there might be a better way to assess the likelihood of metastasis. The team used a murine model of prostate cancer, on which they performed transcriptomic and whole-exome analyses. That investigation led them to the discovery that bone metastases have a distinct molecular profile from primary tumors.

From there, the authors identified 16 genes that appear to be linked with prostate cancer metastasis. They called the genetic signature META-16.

Next, the investigators set out to see whether the presence of the genetic signature was predictive of outcomes in humans. They used biopsies from several hundred patients with localized prostate cancer and tested them for the presence of META-16. The investigators did not know patient outcomes at the time of the genetic analysis.

They found that the signature was highly effective at predicting both time to metastasis and whether a cancer was likely to respond to anti-androgen therapy, which is commonly used to treat advanced disease.

While they are still refining the test, the investigators said it could be a valuable tool to decide which patients are suitable for active surveillance and which are not.

“If we could know in advance which patients will develop metastases, we could start treatments earlier and treat the cancer more aggressively,” said Cory Abate-Shen, PhD, the study’s senior author. “Conversely, patients whose disease is likely to remain confined to the prostate could be spared from unnecessary therapy.”

Arriaga added that knowledge of META-16 could also lead to new therapeutic approaches.

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

The investigators said they hope to evaluate their test, once finished, in a prospective clinical trial.

Reference

Arriaga JM, Panja S, Alshalalfa M, et al. A MYC and RAS co-activation signature in localized prostate cancer drives bone metastasis and castration resistance. Nat Cancer. 2020.1(11) 1082–1096. doi: 10.1038/s43018-020-00125-0