Chemical clues. Metabolites in three classes of tissue

Sreekumar et al., Nature 457, 912 (2009)

A Urine Test for Prostate Cancer?

Oncologists who treat prostate cancer have long been frustrated by a quagmire: They know they treat many men whose disease won't harm them, but at the same time they fail to catch aggressive cases that kill. There's no good way to separate the two right now, but in tomorrow's issue of Nature, a team at the University of Michigan, Ann Arbor, suggests a new strategy: Look for specific chemicals in urine that could distinguish among patients with no sign of disease, disease that isn't critical to treat, and disease that's most dangerous.

Researchers have poured tremendous energy into early cancer detection and forecasting a cancer's path. Hundreds of studies have been published on the use of gene expression or protein analysis, but few tests have reached the clinic. Even those that have, such as an early-detection test for ovarian cancer called OvaSure, which picks up protein patterns, have been criticized for not being adequately tested. In prostate cancer, which kills nearly 30,000 men in the United States each year, "there's been a lot of screening, and people still die," says Ian Thompson, a urologic oncologist at the University of Texas Health Science Center in San Antonio. The community is "desperate," he says, for ways to identify life-threatening tumors.

The Michigan team turned to an approach called metabolomics, a mouthful that refers to the study of small molecules known as metabolites, chemical products present throughout the body. The group screened 100 samples each of men's urine and blood, stored from patients at the cancer center, that were matched with tissue samples that had been removed from patients. Sixteen had no disease, 12 had localized prostate cancer, and 14 had metastatic cancer. The scientists identified 1126 metabolites, then winnowed the list down to six whose levels were higher in samples linked to localized prostate cancer and higher still in metastatic disease. "We were literally going in and measuring everything we could see," says Christopher Beecher, a chemist at the University of Michigan and a co-author of the study.

The group focused on one metabolite in particular, called sarcosine, which may influence cell mobility and which, when added to cells in the lab, transformed normal prostate cells into invasive ones. Seventy-nine percent of metastatic samples contained sarcosine, compared with 42% in localized disease and none in healthy tissue. The researchers hope to devise a simple urine test to pick up the worst prostate cancers at an early stage. Some of the authors have a stake in a company, Metabolon, which is working to commercialize the findings.

It will be years before that can happen, however. The metabolites need to be studied in many men who are followed long-term to see how they measure in those who develop different forms of prostate cancer. Sarcosine in this case was also "not much better" at picking up aggressive disease than prostate-specific antigen, the protein now widely used in screening, says Cory Abate-Shen, a cancer biologist at Columbia University. Still, says Abate-Shen, the strategy is promising: "This hasn't been done before for any cancer."