Metabolic Markers of Early-Stage Pancreatic Cancer
Researchers have identified a marker of early-stage pancreatic cancer that might be used to detect the disease in its initial, more treatable stages.
Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, has been linked with obesity and glucose intolerance, but few studies have evaluated levels of circulating metabolites and cancer progression.
Using samples from 4 prospective cohort studies, Jared R Mayers et al profiled more than 100 metabolites in plasma samples collected from 1500 people before they were diagnosed with pancreatic cancer, reported Medical News Today. They also collected samples from matched individuals who did not develop cancer (controls).
In the online Sept. 28 Nature Medicine, Mayers et al report a 2-fold increase in levels of branched-chain amino acids in plasma samples from people who went on to develop pancreatic cancer, compared with controls. The increase was independent of predisposing factors; the strongest association was observed in subjects whose samples were collected 2 to 5 years before diagnosis, when occult disease is probably present.
However, the length of time between increases in branched-chain amino acids and pancreatic cancer diagnosis ranged from 2 to 25 years, reported HealthDay.
Mayers et al. found that plasma levels of branched-chain amino acids also increased in mice that developed early-stage pancreatic cancer via expression of mutant Kras, but not in mice with Kras-induced tumors in other tissues.
Breakdown of tissue protein appeared to cause the increase in branched-chain amino acids that accompanied early-stage disease. Mayers et al propose that increased whole-body breakdown of protein is an early event in development of PDAC. They suggest that muscle protein loss occurs much earlier in disease progression than previously appreciated.
The study’s senior author, Brian Wolpin (Dana-Farber Cancer Institute) explained in a press release that most people with PDAC receive their diagnosis after the disease has reached an advanced stage, and that many die within a year of diagnosis. “Detecting the disease earlier in its development may improve our ability to treat it,” Wolpin explained.