medwireNews: A nanoparticle-based assay that detects tumor-derived extracellular vesicles (EVs) in plasma samples could not only improve pancreatic cancer diagnosis, but also aid treatment monitoring, say researchers who conducted a proof-of-concept study.
They point out that EVs are released by most cells, but current methods for isolating these vesicles and identifying whether they originated from healthy or cancerous tissues are “impractical for clinical and research use since they require relatively large sample volumes, are complex, low-throughput and expensive, and have long turnaround times.”
Therefore, the study authors developed an alternative approach, nanoplasmon-enhanced scattering (nPES), which is “rapid, ultrasensitive and inexpensive.” EVs present in plasma samples are captured by an EV-specific antibody bound to a sensor chip, and then hybridized with two distinct antibodies, one conjugated to gold nanospheres and the other to gold nanorods, they explain. This dual binding brings the nanospheres and nanorods – which scatter green and red light, respectively – into close proximity, shifting the spectra of scattered light to yellow and also increases scattering intensity.
However, the diagnostic value of the assay relies on the availability of a tumor-specific EV marker, prompting the researchers to use a proteomics and bioinformatics approach to identify ephrin type-A receptor 2 (EphA2), which is overexpressed on EVs from pancreatic cancer cell lines but not untransformed human pancreas cell lines.
Modifying the nPES assay with an antibody against EphA2 alongside an EV-specific antibody showed significantly higher levels of pancreatic cancer-derived EVs (EphA2-EVs) in plasma samples from 10 patients with pancreatic cancer than from 10 patients with pancreatitis and 10 healthy controls.
And in a validation cohort, the EphA2-EV signal distinguished 49 pancreatic cancer patients from 48 with pancreatitis and 48 healthy controls with an accuracy of 94% and 96%, respectively. The assay could also differentiate patients with early (stage I–II) pancreatic cancer from pancreatitis patients with an accuracy of 93%, rising to 96% for differentiating from healthy controls.
Furthermore, EphA2-EV levels were also associated with response to neoadjuvant chemotherapy and/or chemoradiation, such that post-treatment EV levels were significantly lower in patients with a good or partial response (n=13), but not in poor responders (n=10).
Ye Hu (Houston Methodist Research Institute, Texas, USA) and colleagues note that EphA2-EV levels performed “much better” than circulating carbohydrate antigen 19-9 levels – currently the only clinically accepted pancreatic cancer biomarker – both in terms of diagnosis and treatment monitoring.
“We thus propose that an nPES EphA2-EV blood assay may have significant value as a pancreatic cancer screening test, since a rapid, accurate, non-invasive and inexpensive blood test for early pancreatic cancer diagnosis could improve early detection rates to improve patient outcomes,” they write in Nature Biomedical Engineering, but admit the need for validation in larger, prospective studies.
The authors also highlight that “[t]he nPES platform could also be readily customized to diagnose and monitor other cancers and infections by replacing one or both probes with disease- or cell-type-specific EV markers.”
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