Catharine Paddock PhD
A study that successfully differentiated patients with pancreatic cancer from those with another pancreatic disease using a new biomarker, could lead to a blood test that detects pancreatic cancer early enough for curative surgery to be feasible.
Pancreatic cancer has a very poor survival rate and ranks fourth as a leading cause of cancer deaths in the US, where around 46,000 people a year are diagnosed with the disease.
One reason the disease is so deadly is because by the time it is diagnosed, the tumor is too advanced for surgery to be an option – only about 15% of patients qualify for curative surgery.
However, if pancreatic cancer is spotted early, surgery that boosts chance of survival is more feasible, say researchers from the University of Texas MD Anderson Cancer Center in Houston.
In their study the team shows how a protein released by cancer cells into the bloodstream could be used to screen for early pancreatic cancer.
Cancer cells release the protein – which is coded by the gene glypican-1 (GPC1) – in small virus-sized particles called exomes. The exomes contain a mixture of DNA, RNA and proteins.
Blood test looks for cancer exomes
For the study, the team devised a blood test that looks for exomes enriched with the glypican-1 protein – these cancer exomes are called GPC1+ crExos.
A blood test based on these cancer exomes was able successfully to differentiate patients with pancreatic cancer from patients with another chronic pancreatic disease.
It passed both measures of a successful diagnostic test with top marks: specificity (correctly identifying patients with a disease) and sensitivity (correctly ruling out those without the disease), as senior author Raghu Kalluri, a professor in cancer biology, explains:
“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.”
Prof. Kalluri says levels of the cancer exomes were significantly lower in patients after they had their tumors removed.
Cancer exomes could be a more reliable screen than circulating tumor cells
The study also examined samples from breast cancer patients and found – like the pancreatic cancer patients – they also showed high levels of the GPC1+ crExos.
Prof. Kalluri notes that these protein-enriched exomes can be detected in blood samples that have been kept frozen for nearly 30 years. You can’t do this with circulating tumor cells (CTCs) – they require large amounts of fresh blood, he says.
He explains that these cancer exomes could also be useful in other ways:
“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 team suggests cancer exomes appear to be a more reliable way to screen for pancreatic cancer than using the more common CA 19-9 biomarker test. Using the cancer exome test, they found precancerous lesions in mice bred to develop pancreatic cancer before they could be spotted on magnetic resonance imaging (MRI).
Prof. Kalluri says because they carry cancer-specific genetic material, the protein-enriched exomes could potentially enhance the specificity of MRI or CT scans, and concludes:
“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. This presents an unprecedented opportunity for informative early detection of pancreatic cancer and in designing potential curative surgical options.”
As well as the MD Anderson Cancer Center, The Cancer Prevention and Research Institute of Texas, and the National Cancer Institute (part of the by the National Institutes of Health) provided funds for the study.