Multiparametric plasma EV profiling facilitates diagnosis of pancreatic malignancy

作者:Yang Katherine S; Im Hyungsoon; Hong Seonki; Pergolini Ilaria; del Castillo Andres Fernandez; Wang Rui; Clardy Susan; Huang Chen Han; Pille Craig; Ferrone Soldano; Yang Robert; Castro Cesar M; Lee Hakho; del Castillo Carlos Fernandez; Weissleder Ralph
来源:Science Translational Medicine, 2017, 9(391): eaal3226.
DOI:10.1126/scitranslmed.aal3226

摘要

<jats:p>Pancreatic ductal adenocarcinoma (PDAC) is usually detected late in the disease process. Clinical workup through imaging and tissue biopsies is often complex and expensive due to a paucity of reliable biomarkers. We used an advanced multiplexed plasmonic assay to analyze circulating tumor-derived extracellular vesicles (tEVs) in more than 100 clinical populations. Using EV-based protein marker profiling, we identified a signature of five markers (PDAC<jats:sup>EV</jats:sup>signature) for PDAC detection. In our prospective cohort, the accuracy for the PDAC<jats:sup>EV</jats:sup>signature was 84% [95% confidence interval (CI), 69 to 93%] but only 63 to 72% for single-marker screening. One of the best markers, GPC1 alone, had a sensitivity of 82% (CI, 60 to 95%) and a specificity of 52% (CI, 30 to 74%), whereas the PDAC<jats:sup>EV</jats:sup>signature showed a sensitivity of 86% (CI, 65 to 97%) and a specificity of 81% (CI, 58 to 95%). The PDAC<jats:sup>EV</jats:sup>signature of tEVs offered higher sensitivity, specificity, and accuracy than the existing serum marker (CA 19-9) or single–tEV marker analyses. This approach should improve the diagnosis of pancreatic cancer.</jats:p>