A compound called sarcosine may distinguish slow-growing prostate cancers from those likely to spread and become lethal, a new study shows. And in an unexpected finding, benign prostate cells take on cancerous characteristics in lab dishes when exposed to sarcosine, suggesting that the compound is less of a bystander and more of a perpetrator in the malignancy, researchers report in the Feb. 12 Nature.
“It’s not only a biomarker for aggressive prostate cancer, but it might be involved in the biology of the cancer,” says study coauthor Arul Chinnaiyan, a Howard Hughes Medical Institute investigator and pathologist at the University of Michigan in Ann Arbor.
Tests for elevated sarcosine also outperformed the most widely used clinical test for detecting prostate cancer. Conveniently, sarcosine can be identified in urine, a less invasive test than the blood analysis needed for the standard prostate-specific antigen, or PSA, test routinely given to men to check for signs of cancer.
To arrive at these findings, Chinnaiyan and his team analyzed 1,126 metabolites in samples of prostate tissue, blood and urine obtained from men with various stages of prostate cancer and from a group of men without the cancer. Sarcosine was undetectable in healthy tissue but turned up in large amounts in prostate cancer confined to the gland and in even greater levels in metastatic cancer.
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A separate test showed that sarcosine levels in urine were much higher in men with prostate cancer than in men without it.
And when compared with a PSA test, sarcosine levels were “at least as good, and perhaps better, than PSA” in identifying the presence and aggressiveness of cancer, says study coauthor John Wei, a urologist at the University of Michigan.
Five other compounds also appeared in large concentrations in metastatic prostate cancer. By measuring concentrations of these compounds, doctors might someday be better able to diagnose prostate cancer and distinguish dangerous malignancies from cancer that’s unlikely to leave the prostate, the findings suggest.
Prostate cancer diagnosis is an imprecise science, says William Isaacs, a molecular biologist at the Johns Hopkins University School of Medicine in Baltimore. The typical exam combines a digital probe of the prostate to check for swelling or lumps and a blood test to reveal PSA levels. This one-two punch turns up many prostate cancers that would have gone undetected decades ago, but quite often men have PSA scores that fall into a gray area, he says. Biopsy is needed to clarify a diagnosis.
But even when a biopsy reveals cancer, it sometimes remains unclear whether the cancer is aggressive and at risk of spreading, or indolent and likely to stay put. For example, a biopsy might sample a part of the prostate with little cancer and underestimate the danger, says Cory Abate-Shen, a cancer biologist at Columbia University College of Physicians and Surgeons. So biopsy doesn’t always reveal who needs aggressive treatment, she says.
“There’s no question we need better markers,” Isaacs says. Whether sarcosine or some of the other metabolites identified in the new study will fit the bill remains to be seen. “I think people will try to repeat this work and try to get it into the clinic as fast as possible,” he says.
Meanwhile, the study authors were surprised to find that sarcosine, a metabolite of the amino acid glycine, might also play a role in abetting cancer itself. When they added sarcosine to benign prostate cells in lab-dish experiments, the cells showed cancerous behavior. Chinnaiyan expects animal experiments to clarify any direct role sarcosine might play in prostate cancer.
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Ideally, such research would reveal points at which scientists might intercede in the cancer process.
The study is also noteworthy because it goes beyond the study of genes (genomics) and proteins (proteomics) to delve into metabolomics — the study of metabolites, Abate-Shen says. Metabolites are the end products of cell processes, and much might be learned from these compounds, she says. “But it’s not like they have a genetic code,” she says, “so it’s technically challenging.”
In the 1950s and 1960s, metabolites were a hot research topic as scientists tried to figure out the roles of enzymes in cell biology, Isaacs says. Times change and metabolites were largely set aside in favor of genes, DNA, RNA and proteins — at least in the search for biomarkers, he says. With the new study, he says, “hopefully we’ll get some sort of re-emergence of people interested in metabolites. I think it’s a really important study from that point of view.”