Genetic signatures for aggressive prostate cancer identified

By Nikki Withers, medwireNews Reporter

Researchers have identified two genetic signatures for castration-resistant prostate cancer that may predict the severity of the disease.

The findings appear in two separate studies published in The Lancet Oncology.

In the first study, William Oh (Mount Sinai School of Medicine, New York, USA) and colleagues assessed the effectiveness of whole-blood RNA transcript profiling for predicting survival in 62 men with castration-resistant prostate cancer.

The team identified a set of six genes (consisting of ABL2, SEMA4D, ITGAL, C1QA, TIMP1, and CDKN1A) that were able to predict survival. The signature divided patients into two risk groups: one with a median survival time of 7.8 months (high risk) and the other with a median survival of at least 24 months (low risk). A validation cohort of 140 patients confirmed these findings.

In the second study, Johan de Bono (The Royal Marsden NHS Federation Trust, Sutton, UK) and colleagues used microarray-based expression profiling of whole-blood samples from 64 men with advanced castration-resistant prostate cancer and 30 patients with prostate cancer on active surveillance to identify expression patterns specific for aggressive disease.

They identified a set of nine genes that stratified patients with castration-resistant prostate cancer. Patients who had the nine-gene pattern survived for an average of 9.2 months after referral for treatment compared with 21.6 months for patients who did not test positive for the signature.

Scarcity of prognostic markers has previously presented a major challenge for the clinical management of castration-resistant prostate cancer and for stratification of patients into clinical trials.

Indeed, De Bono and co-authors say that biomarkers are "urgently needed to dissect the heterogeneity of prostate cancer between patients to improve treatment and accelerate drug development." In their study they conclude that gene-expression signatures may have "significant prognostic value" in the future.

In an accompanying comment, Karina Dalsgaard Sørensen, from Aarhus University Hospital in Denmark, said: "These results suggest that a few selected genes in blood samples from patients with castration-resistant prostate cancer can significantly improve the prediction outcomes."

However, she warned that the biologic relevance of these prognostic signatures, which are the first of their kind, is largely unknown. "Further investigation into the underlying biological mechanisms at work here could greatly advance our understanding," she concluded.

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