Research ArticleCancer

Multiparametric plasma EV profiling facilitates diagnosis of pancreatic malignancy

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Science Translational Medicine  24 May 2017:
Vol. 9, Issue 391, eaal3226
DOI: 10.1126/scitranslmed.aal3226

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A signature achievement

Pancreatic ductal adenocarcinoma is one of the deadliest types of tumors, in part because it is usually detected at a late stage. To facilitate the diagnosis of this tumor, Yang et al. developed a multiplexed plasmonic assay to evaluate extracellular vesicles in patient plasma for protein markers associated with the presence of pancreatic cancer. The authors identified a five-marker signature that yielded the most accurate diagnosis. To test their assay, the researchers analyzed samples from patients with pancreatic cancer and other types of pancreatic disease, as well as healthy controls, and confirmed the accuracy of their signature in prospectively collected samples.

Abstract

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

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