Exosome Protein Useful for Early Pancreatic Cancer Detection

June 25, 2015
Exosome Protein Useful for Early Pancreatic Cancer Detection
Artistic interpretation of an exosome carrying DNA/RNA from a cancer cell. [National Institutes of Health]

Precision noninvasive screening tools are paramount to diagnostic medicine for the early detection of potentially life-threating diseases. Now, researchers at The University of Texas MD Anderson Cancer Center have found a protein present on exosomes, which they believe could become a standard diagnostic biomarker for pancreatic cancer.

Typically, exosomes contain DNA, RNA, and protein molecules that often end up within the systemic circulation of patients suffering from cancer. In the current study, scientists were able to isolate and monitor exosomes containing a protein encoded by the glypican-1 gene (GPC1) from the blood of pancreatic cancer patients, which the researchers dubbed, GPC1 + crExos.  

"GPC1+ 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," explained senior author Raghu Kalluri, M.D., Ph.D., chair of Cancer Biology at MD Anderson.

The findings from this study were published recently in Nature through an article entitled "Glypican-1 identifies cancer exosomes and detects early pancreatic cancer."

Interestingly, the levels of GPC1+ crExos were significantly lower in patients following surgical removal of the tumor. Moreover, the study examined crExos from healthy donors as well as breast and pancreatic cancer patients—with elevated GPC1+ crExos being observed in both cancers. 

Exosomes represent a versatile and advantageous tool for the study of various cancers, as the vesicles and their contents are relatively stable for long periods of time.

"GPC1+ crExos can be detected and isolated in blood samples that were stored in freezers almost 30 years ago, unlike circulating tumor cells (CTCs) 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."

The MD Anderson team made a critical observation once all the results from the current study were fully analyzed, which was that GPC1+ crExos appeared to be a more reliable screening tool than the commonly used CA 19-9 biomarker. Astonishingly, while screening for GPC1+ crExos, the investigators were able to detect the possibility of pancreatic cancer in mouse models at a time when the mice showed no signs of pancreatic disease by MRI.

"Routine screening of the general population for pancreatic cancer using MRIs or CTs would be prohibitively expensive with the likelihood for many false positives," stated co-author David Piwnica-Worms, M.D., Ph.D., chair of Cancer Systems Imaging at MD Anderson. "Our study suggests the potential for GPC1+ crExos as a detection and monitoring tool for pancreatic cancer in combination with imaging, with an emphasis on its application in early detection."

Recent data concerning pancreatic cancer suggests that early detection could be lifesaving as more patients would qualify for surgeries shown to be curative. Since pancreatic cancer is often diagnosed in more advanced stages, only about 15% of patients currently qualify for any type of 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."