Dr. Stuart Ibsen, Oregon Health and Science University
Host: Dr. Anand
Tumors shed different types of nanoparticles containing valuable cancer biomarkers into circulation throughout their development. One major class of shed particles are extracellular vesicles, such as exosomes, that contain protein biomarkers. A second class are nanoparticles comprised of cell-free DNA (cfDNA) containing cancer related mutations. Despite their importance, these two particle types are a challenge to use in clinical cancer screening applications because they are difficult to recover from plasma using traditional methods. To address this challenge, we have developed a method using high conductance dielectrophoresis (DEP) chip technology that can simultaneously collect both types of particles quickly from undiluted plasma. A buffer wash removes the bulk plasma purifying the desired nanoparticles. This enables quantifiable immunostaining of protein biomarkers on the vesicles and fluorescent dye staining of the cfDNA. We show the cfDNA can also be recovered and analyzed using digital PCR to detect cancer related mutations. We applied this technique in a blinded study that analyzed plasma samples from a 36 patient cohort consisting of patients with pancreatic cancer and benign pancreatic disease. Based on the relative levels of the protein biomarker Glypican 1 and the overall level of cfDNA we were able to use a bivariate analysis to successfully differentiate patients with pancreatic cancer from patients with benign pancreatic diseases such as pancreatitis, precancerous intraductal papillary mucinous neoplasm (IPMN), and healthy individuals making it a promising technique for future clinical translation.