Journal
CELL
Volume 182, Issue 4, Pages 1044-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2020.07.009
Keywords
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Categories
Funding
- NIH Shared Instrumentation Grant [S10RR027699]
- National Cancer Institute [CA224175, CA210240, CA232093, CA163117, CA207983, CA163120, CA169416, CA169538, CA218513, AI144301]
- United States Department of Defense [W81XWH-13-1-0425, W81XWH-13-1-0427, W81XWH-13-1-0249, W81XWH-14-1-0199]
- Melanoma Research Alliance
- Hartwell Foundation
- Thompson Family Foundation
- STARR Consortium [I9-A9-056, I8-A8-123]
- Pediatric Oncology Experimental Therapeutics Investigator's Consortium
- Alex's Lemonade Stand Foundation
- Breast Cancer Research Foundation
- Feldstein Medical Foundation
- Tortolani Foundation
- Clinical & Translational Science Center
- Mary Kay Ash Charitable Foundation
- Malcolm Hewitt Weiner Foundation
- Manning Foundation
- Daniel P. and Nancy C. Paduano Family Foundation
- James Paduano Foundation
- Sohn Foundation
- AHEPA Vth District Cancer Research Foundation
- Daedalus Fund
- Selma and Lawrence Ruben Science to Industry Bridge Award
- Children's Cancer and Blood Foundation
- Scott and Lisa Stuart Family Foundation
- D10 Foundation
- Susan G. Komen Postdoctoral Fellowship [PDF15331556]
- Susan G. Komen Postdoctoral Fellowship (JST PRESTO) [30021]
- Susan G. Komen Postdoctoral Fellowship (JSPS KAKENHI) [JP19K23743]
- National Research Foundation of Korea [2019R1C1C1006709, 2018R1A5A2025079]
- Severance Hospital Research fund for Clinical Excellence [C-2019-0026]
- Yonsei University College of Medicine [6-2019-0090]
- Daewoong Foundation Research Grant
- Swedish Cancer Society Pancreatic Cancer Fellowship
- Lions International Postdoctoral fellowship
- Sweden-America stipend
- Memorial Sloan Kettering Cancer Center Metastasis and Tumor Ecosystems Center fellowship
- Weill Cornell Medical College Clinical and Translational Science Center - NIH/NCATS [UL1TR002384]
- Little Eric Foundation
- EVAN Foundation
- National Research Foundation of Korea [2019R1C1C1006709] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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There is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of extracellular vesicles and particles (EVPs) in 426 human samples from tissue explants (TEs), plasma, and other bodily fluids. Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers. To confirm that EVPs are ideal diagnostic tools, we analyzed proteomes of TE- (n =151) and plasma-derived (n =120) EVPs. Comparison of TE EVPs identified proteins (e.g., VCAN, TNC, and THBS2) that distinguish tumors from normal tissues with 90% sensitivity/94% specificity. Machine-learning classification of plasma-derived EVP cargo, including immunoglobulins, revealed 95% sensitivity/90% specificity in detecting cancer Finally, we defined a panel of tumor-type-specific EVP proteins in TEs and plasma, which can classify tumors of unknown primary origin. Thus, EVP proteins can serve as reliable biomarkers for cancer detection and determining cancer type.
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