Simple Blood Test for early detection of pancreatic cancer

The researchers at University of California, San Diego, California have developed a new diagnostic test that shows promise for early detection of pancreatic cancer. The test, which is at the proof-of-concept stage, can rapidly screen a drop of blood for biomarkers of the disease that provide results in less than an hour. The findings are published in the journal ACS Nano.

The study was conducted by Jean M. Lewis, an assistant project scientist in the Department of Nanoengineering at UC San Diego, and colleagues to develop a diagnostic test for early detection of pancreatic cancer.

Pancreatic cancer is associated with poor survival and ranked as the fourth or fifth most common cause of cancer mortality, despite its low incidences. This is because the disease is not detected until it has reached an advanced stage and thus becomes difficult to cure.

"An important step towards being able to cure diseases that come out of nowhere, like pancreatic cancer, is early detection," said first author Jean Lewis. "We envision that in the future, physicians might perform this type of test using a quick finger stick to diagnose patients who may not know they have the disease yet."

Liquid biopsies, blood tests for early cancer detection, are a hot topic in research. The tests hold potential for early detection of cancer eliminating the need for invasive surgical procedures like tumor biopsies.

This new method developed for early detection of pancreatic cancer involves capture and analysis of nano-sized biological structures called exosomes, which are nanoscale vesicles shed into the blood from tumors. They contain proteins and genetic material that can serve as biomarkers for detecting cancers. However, their isolation from the blood is difficult due to their tiny and fragile nature.

The test developed by UC San Diego researchers uses an electronic chip-based system to extract exosomes directly from blood in minutes. "We can use just a drop of blood as is--no extra processing required," said Lewis. "We can also analyze the exosomes right there on the spot and show whether they carry any of the cancer biomarkers we are looking for."

The test is simple. Apply a drop of blood on a small electronic chip, turn the current on, wait several minutes, add fluorescent labels and look at the results under a microscope. If a blood sample tests positive for pancreatic cancer, bright fluorescent circles will appear.

"This test could be used as a primary screening strategy to identify patients who would subsequently need to undergo more expensive and invasive diagnostic methods like a CT scan, MRI or endoscopy," said Dr. Rebekah White, surgical oncologist and associate professor of surgery at Moores Cancer Center.

The chip used in this test works by applying an alternating electric current, which selectively pulls nano-sized particles like exosomes out of the blood and deposits them onto tiny electrodes on the chip's surface. Larger blood particles get washed away while smaller ones such as exosomes are left behind. Researchers then apply fluorescently labeled antibodies that specifically target two protein biomarkers for pancreatic cancer: glypican-1 and CD63. If these biomarkers are present, brightly colored circles where the antibodies bind can be seen under a microscope, indicating a positive result. This entire process can be done in less than an hour.

"Future work would entail obtaining blood samples from patients that have high-risk factors for pancreatic cancer--new-onset diabetes or a family history of it, smoking or obesity--and continue sampling their blood over an extended period of time. Of the patients that are subsequently diagnosed, we can go back and analyze their pre-diagnostic blood samples to see how early on we can detect cancer biomarkers," said White.

In the current ACS Nano paper, UC San Diego researchers used the exosome-isolating capability of molecular diagnostics company Biological Dynamics to develop a custom assay for pancreatic cancer detection.

This system is tested on a small sample set of patients. In an initial validation study on a group of 31 patients, the chip was able to flag the blood samples of 20 patients with pancreatic cancer from those of 11 patients without cancer.

Next steps also include studies on a larger sample size, screening more samples from patients at various stages of cancer, and optimizing and validating this technology for early cancer detection. "A challenge in doing these studies is getting hold of early-stage blood samples when patients don't even know they have the disease yet," said Lewis.

The researchers are also exploring other blood-based biomarkers--in addition to glypican-1 and CD63--to improve this system's accuracy and sensitivity for pancreatic cancer detection.