Protein-Enriched Exosome Useful for Early Diagnosis of Pancreatic Cancer
A protein encoded by the gene glypican-1 (GPC1) present on cancer exosomes may be used as part of a potential noninvasive diagnostic and screening tool to detect early pancreatic cancer, potentially at a stage amenable to surgical treatment, according to a study completed by University of Texas MD Anderson Cancer Center researchers. Their findings were published by Melo et al in Nature.
Reliable Detection
Scientists isolated and monitored GPC1-enriched circulating exosomes from the blood of patients with pancreatic cancer, termed GPC1-positive crExos.
“GPC1-positive crExos were detected in small amounts of serum from about 250 patients with pancreatic cancer with absolute specificity and sensitivity, importantly distinguishing patients with chronic pancreatitis from those with early- and late-stage pancreatic cancer,” said Raghu Kalluri, MD, PhD, Chair of Cancer Biology at MD Anderson.
Levels of GPC1-positive crExos were significantly lower in patients following surgical removal of the tumor, said Dr. Kalluri. The study examined crExos from healthy donors, as well as patients with breast and pancreatic cancers. Elevated GPC1-positive crExos were seen in both cancers.
“GPC1-positive crExos can be detected and isolated in blood samples that were stored in freezers almost 30 years ago, unlike circulating tumor cells that require large amounts of fresh blood,” said Dr. Kalluri. “DNA, RNA, and proteins can be isolated from cancer exosomes isolated from stored specimen for further genetic and biological analyses. Therefore, cancer exosomes are not just a biomarker, but isolating them provides a trove of cancer specific information.”
Potential for Early Detection
GPC1-positive crExos appear to be a more reliable pancreatic cancer screening tool than the commonly used CA 19-9 biomarker. The study found that GPC1-positive crExos detected the possibility of pancreatic cancer in mouse models at a time when the mice showed no signs of pancreatic disease by magnetic resonance imaging (MRI).
“Routine screening of the general population for pancreatic cancer using MRIs or computerized tomography (CT) would be prohibitively expensive, with the likelihood for many false positives,” said David Piwnica-Worms, MD, PhD, Chair of Cancer Systems Imaging at MD Anderson. “Our study suggests the potential for GPC1-positive crExos as a detection and monitoring tool for pancreatic cancer in combination with imaging, with an emphasis on its application in early detection.”
“Because pancreatic cancer-specific genetics can be detected in these exosomes, there is great potential to enhance specificity of MRIs or CTs,” said Dr. Kalluri.
If pancreatic cancer is detected early, surgery involving a pancreaticoduodenectomy or the Whipple procedure can be curative. Since pancreatic cancer is often diagnosed in the later stages, only about 15% of patients qualify for such surgery.
“Studies comparing stage of disease with outcome following surgery suggest that death rates for pancreatic cancer would be reduced if the disease were diagnosed at an earlier stage,” said Dr. Kalluri. “This presents an unprecedented opportunity for informative early detection of pancreatic cancer and in designing potential curative surgical options.”
The study was funded by the Cancer Prevention and Research Institute of Texas, MD Anderson Cancer Center, and the National Institutes of Health/National Cancer Institute.
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