Quantitative Proteomic Analysis of Serum Exosomes from Patients with Locally Advanced Pancreatic Cancer Undergoing Chemoradiotherapy

Pancreatic cancer
is the third leading cause of cancer-related
death in the USA. Despite extensive research, minimal improvements
in patient outcomes have been achieved. Early identification of treatment
response and metastasis would be valuable to determine the appropriate
therapeutic course for patients. In this work, we isolated exosomes
from the serum of 10 patients with locally advanced pancreatic cancer
at serial time points over a course of therapy, and quantitative analysis
was performed using the iTRAQ method. We detected approximately 700–800
exosomal proteins per sample, several of which have been implicated
in metastasis and treatment resistance. We compared the exosomal proteome
of patients at different time points during treatment to healthy controls
and identified eight proteins that show global treatment-specific
changes. We then tested the effect of patient-derived exosomes on
the migration of tumor cells and found that patient-derived exosomes,
but not healthy controls, induce cell migration, supporting their
role in metastasis. Our data show that exosomes can be reliably extracted
from patient serum and analyzed for protein content. The differential
loading of exosomes during a course of therapy suggests that exosomes
may provide novel insights into the development of treatment resistance
and metastasis.