Four-Gene Signature Predicts Aggressive Prostate Cancer

In a study reported in Nature online on February 2, researchers describe a four-gene signature that was more accurate than the standard Gleason score test in predicting which patients would die from metastatic spread of their prostate cancer. The Gleason score is about 60% to 70% accurate in predicting whether a man’s prostate cancer will become aggressive. In the Nature study, the four-gene signature alone was 83% accurate in making this prediction, and 92% accurate when combined with the Gleason score.

The four genes used in the test are Pten, Smad4, SPP1, and CyclinD1. Mouse and human studies were assessed to identify genes that promoted aggressive growth of prostate tumors, using computational biology, genetically engineered model systems, molecular and cellular biology, and human tissue microarrays, noted lead investigator Ronald DePinho, MD, of Dana-Farber Cancer Institute’s Belfer Institute for Applied Cancer Science.

The discovery provides a foundation for developing the first gene-based test to determine whether a man’s prostate cancer is likely to remain dormant within the prostate gland, or instead spread aggressively to other parts of the body. Such a test has the potential to spare many men from unnecessary treatment for prostate cancers that may never kill them, given that the majority of prostate cancers are not life-threatening, even if untreated, Dr. DePinho noted. It is also of great benefit to be spared the physical effects of unnecessary treatment, he said, since surgery and radiation therapy for prostate cancer can have long-lasting complications, including impotence and urinary problems such as incontinence.

The investigators tested the four-gene signature in hundreds of human prostate tumor tissue samples taken from the Physicians’ Health Study, a 30-year study of US physicians. Dana-Farber has licensed the technology to Metamark Genetics Inc, a Massachusetts-based company that will commercialize the test. The goal is to make the test available in about a year or so, said Dr. DePinho, who, with study author Lynda Chin, MD, is a co-founder of Metamark. The study was funded by the Belfer Institute for Applied Cancer Science and the National Cancer Institute.