Multiparametric plasma EV profiling facilitates diagnosis of pancreatic malignancy

• Published in: Science translational medicine Vol. 9; no. 391
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States 24-05-2017
• Subjects: Biomarkers, Tumor - blood; CA-19-9 Antigen - blood; Carcinoma, Pancreatic Ductal - blood; Carcinoma, Pancreatic Ductal - diagnosis; Female; Humans; Male; Pancreatic Neoplasms; Pancreatic Neoplasms - blood; Pancreatic Neoplasms - diagnosis; Prospective Studies
• ISSN: 1946-6242
• DOI: 10.1126/scitranslmed.aal3226

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
signature) for PDAC detection. In our prospective cohort, the accuracy for the PDAC
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
signature showed a sensitivity of 86% (CI, 65 to 97%) and a specificity of 81% (CI, 58 to 95%). The PDAC
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.