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Sci Transl Med. 2017 May 24;9(391). pii: eaal3226. doi: 10.1126/scitranslmed.aal3226.

Multiparametric plasma EV profiling facilitates diagnosis of pancreatic malignancy.

Author information

1
Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
2
Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA.
3
Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
4
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
5
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA 02215, USA.
6
Department of Health Sciences, Northeastern University, Boston, MA 02115, USA.
7
Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA.
8
Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114, USA. rweissleder@mgh.harvard.edu.
9
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.

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.

PMID:
28539469
PMCID:
PMC5846089
DOI:
10.1126/scitranslmed.aal3226
[Indexed for MEDLINE]
Free PMC Article

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