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Pancreatic Cancer Study Finds Possible Diagnostic Marker in Blood

, by NCI Staff

Exosomes containing the protein GPC1 could potentially be used to detect early signs of pancreatic cancer in blood, according to a new study.

Credit: Macmillan Publishers Ltd, Nature

Researchers have identified a potential biological marker for detecting pancreatic cancer in its early stages—a protein attached to vesicles that circulate in blood. The findings appeared June 24 in Nature.

All cells—including cancer cells—release extracellular vesicles, or exosomes, which contain proteins, DNA, and RNA. These nano-sized sacs may enter the bloodstream and travel around the body, interacting with other cells.

For a decade, researchers have been exploring the use of exosomes as potential markers for various diseases, including pancreatic cancer, which is often detected in its advanced stages. The new study used flow cytometry to show that exosomes released by pancreatic cancer cells have a cell surface protein called glypican-1 (GPC1) that is not found on exosomes shed by other cells.

“We developed a method of detecting exosomes from pancreatic cancer cells in blood, and we used the method to identify patients with the disease,” said Raghu Kalluri, M.D., Ph.D., of the University of Texas MD Anderson Cancer Center, who led the study.

To begin, the researchers analyzed blood from 190 patients with pancreatic cancer, 32 patients with breast cancer, 26 patients with benign pancreatic disease, 5 with pancreatic cancer precursor lesions, and 100 healthy donors. Compared with healthy donors, all of the patients with pancreatic cancer had elevated blood levels of exosomes containing GPC1, whereas only some of the patients with breast cancer did.

Further experiments suggested that GPC1 could be a marker for early disease. Levels of exosomes containing GPC1 were consistently higher among 5 patients with pancreatic cancer precursor lesions than among healthy donors or 26 patients with benign pancreatic disease, such as chronic pancreatitis. In mouse models of pancreatic cancer, elevated levels of exosomes containing GPC1 were detected earlier than the disease could be found through imaging studies.

The researchers validated their findings in an independent cohort, which included 6 patients with chronic pancreatitis, 56 patients with pancreatic cancer, and 20 healthy donors. Based on all of the results, the study authors concluded that exosomes containing GPC1 could be used to develop a noninvasive diagnostic test for early pancreatic cancer.

“Although the number of patients in the precancerous-lesion group was low, and the findings require further validation in a larger cohort, the potential implications of such a test are huge,” Clotilde Théry, Ph.D., who studies extracellular vesicles and cancer at the Institut Curie, Paris, wrote in an accompanying editorial.

“This work demonstrates for the first time that circulating vesicles in blood can be a source of specific and reliable diagnostic biomarkers for cancer,” Dr. Théry added.

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