Branched Chain Amino Acids Levels Spike Years Before Pancreatic Cancer Diagnosis

Christine Daniloff/MIT

Pancreatic cancer is aggressive and hard to spot early, which has contributed to it being the number four cause of cancer death in the United States. Those who have been diagnosed with pancreatic ductal adenocarcinoma (PDAC) typically do not last longer than a year. A team of researchers led by Matthew Vander Heiden of MIT looked back at previous blood plasma samples in patients who had been diagnosed with PDAC in order to find any early warning signs, and discovered that certain amino acids increased several years prior to the pancreatic cancer diagnosis. The paper was published in Nature Medicine.

Vander Heiden’s team used blood plasma samples from 1500 participants of unrelated long-term health studies. With hindsight being 20/20, the team would search for any anomalies between the samples provided prior to a diagnosis of PDAC. They found that patients whose samples showed spiked levels of branched chain amino acids (BCAA) were twice as likely to become diagnosed with the disease within 1 to 10 years, compared to those who did not.

“Pancreatic cancer, even at its very earliest stages, causes breakdown of body protein and deregulated metabolism. What that means for the tumor, and what that means for the health of the patient — those are long-term questions still to be answered,” Vander Heiden said in a press release.

As the pancreas produces many hormones that aid in digestion and metabolism, Vander Heiden’s team was looking for unchecked levels among hundreds of metabolite byproducts, like protein, vitamins, sugar, and alcohol. The key turned out to be a building block of protein: amino acids. There are 20 amino acids which can be utilized by the body in many different ways to make thousands of different proteins for the body. BCAA are set apart by the aliphatic side chains within their molecular structure

“What we found was that this really interesting signature fell out as predicting pancreatic cancer diagnosis, which was elevation in these three branched chain amino acids: leucine, isoleucine, and valine,” Vander Heiden explained.

The team explored this hypothesis using mice destined to develop pancreatic cancer, monitoring the levels of BCAA within their blood to predict the onset of the disease.

 “Using those mouse models, we found that we could perfectly recapitulate these exact metabolic changes during the earliest stages of cancer,” Vander Heiden continued. “What happens is, as people or mice develop pancreatic cancer, at the very earliest stages, it causes the body to enter this altered metabolic state where it starts breaking down protein in distant tissues.”

While this is not the first study to draw a connection between pancreatic distress and increased levels of BCAA, this is the first to check back through a patient’s history and find when the levels began to increase. As PDAC is typically diagnosed fairly late in the disease’s progression, identifying abnormal levels of metabolite markers could be used as a way to spot the disease early, when it could best be treated. As of now, BCAA levels alone are not an accurate predictor of disease, though the researchers believe more biomarkers could be identified in the future.

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