2. Academic Validation
  3. Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers

Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers

  • Cell. 2020 Aug 20;182(4):1044-1061.e18. doi: 10.1016/j.cell.2020.07.009.
Ayuko Hoshino 1,  Han Sang Kim 2,  Linda Bojmar 3,  Kofi Ennu Gyan 4,  Michele Cioffi 5,  Jonathan Hernandez 6,  Constantinos P Zambirinis 7,  Gonçalo Rodrigues 8,  Henrik Molina 9,  Søren Heissel 9,  Milica Tesic Mark 9,  Loïc Steiner 10,  Alberto Benito-Martin 5,  Serena Lucotti 5,  Angela Di Giannatale 11,  Katharine Offer 5,  Miho Nakajima 5,  Caitlin Williams 5,  Laura Nogués 12,  Fanny A Pelissier Vatter 5,  Ayako Hashimoto 13,  Alexander E Davies 14,  Daniela Freitas 15,  Candia M Kenific 5,  Yonathan Ararso 5,  Weston Buehring 5,  Pernille Lauritzen 5,  Yusuke Ogitani 5,  Kei Sugiura 16,  Naoko Takahashi 17,  Maša Alečković 18,  Kayleen A Bailey 5,  Joshua S Jolissant 7,  Huajuan Wang 5,  Ashton Harris 5,  L Miles Schaeffer 5,  Guillermo García-Santos 19,  Zoe Posner 5,  Vinod P Balachandran 20,  Yasmin Khakoo 21,  G Praveen Raju 22,  Avigdor Scherz 23,  Irit Sagi 24,  Ruth Scherz-Shouval 25,  Yosef Yarden 24,  Moshe Oren 26,  Mahathi Malladi 21,  Mary Petriccione 21,  Kevin C De Braganca 21,  Maria Donzelli 21,  Cheryl Fischer 21,  Stephanie Vitolano 21,  Geraldine P Wright 21,  Lee Ganshaw 21,  Mariel Marrano 21,  Amina Ahmed 21,  Joe DeStefano 21,  Enrico Danzer 27,  Michael H A Roehrl 28,  Norman J Lacayo 29,  Theresa C Vincent 30,  Martin R Weiser 31,  Mary S Brady 32,  Paul A Meyers 21,  Leonard H Wexler 21,  Srikanth R Ambati 21,  Alexander J Chou 21,  Emily K Slotkin 21,  Shakeel Modak 21,  Stephen S Roberts 21,  Ellen M Basu 21,  Daniel Diolaiti 33,  Benjamin A Krantz 34,  Fatima Cardoso 35,  Amber L Simpson 36,  Michael Berger 28,  Charles M Rudin 37,  Diane M Simeone 33,  Maneesh Jain 38,  Cyrus M Ghajar 39,  Surinder K Batra 38,  Ben Z Stanger 40,  Jack Bui 41,  Kristy A Brown 42,  Vinagolu K Rajasekhar 43,  John H Healey 43,  Maria de Sousa 8,  Kim Kramer 21,  Sujit Sheth 44,  Jeanine Baisch 45,  Virginia Pascual 45,  Todd E Heaton 27,  Michael P La Quaglia 27,  David J Pisapia 46,  Robert Schwartz 47,  Haiying Zhang 5,  Yuan Liu 48,  Arti Shukla 49,  Laurence Blavier 50,  Yves A DeClerck 50,  Mark LaBarge 51,  Mina J Bissell 52,  Thomas C Caffrey 38,  Paul M Grandgenett 38,  Michael A Hollingsworth 38,  Jacqueline Bromberg 53,  Bruno Costa-Silva 54,  Hector Peinado 55,  Yibin Kang 18,  Benjamin A Garcia 56,  Eileen M O'Reilly 37,  David Kelsen 37,  Tanya M Trippett 21,  David R Jones 48,  Irina R Matei 5,  William R Jarnagin 57,  David Lyden 58
Affiliations

Affiliations

  • 1 Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA; School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan; Japan Science and Technology Agency, PRESTO, Tokyo, Japan. Electronic address: ayukohoshino@bio.titech.ac.jp.
  • 2 Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA; Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Brain Korea 21 Plus Project for Medical Sciences, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
  • 3 Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA; Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala, Sweden.
  • 4 Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA; Tri-Institutional PhD Program in Computational Biology and Medicine, New York, NY, USA.
  • 5 Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
  • 6 Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA; Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD USA.
  • 7 Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA; Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 8 Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA; Graduate Program in Areas of Basic and Applied Biology, Abel Salazar Biomedical Sciences Institute, University of Porto, Porto, Portugal.
  • 9 Proteomics Resource Center, The Rockefeller University, New York, NY, USA.
  • 10 Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA; Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland.
  • 11 Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA; Department of Pediatric Haematology/Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
  • 12 Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA; Microenvironment and Metastasis Laboratory, Department of Molecular Oncology, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
  • 13 Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA; School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan; Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
  • 14 Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.
  • 15 Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA; i3S-Institute for Research and Innovation in Health, University of Porto, Rua Alfredo Allen 208, Porto, Portugal.
  • 16 School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan; Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
  • 17 School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan.
  • 18 Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
  • 19 Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA; Department of General and Gastrointestinal Surgery, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain.
  • 20 Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 21 Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 22 Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 23 Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot, Israel.
  • 24 Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
  • 25 Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
  • 26 Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
  • 27 Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Pediatric Surgical Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 28 Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 29 Lucile Packard Children's Hospital Stanford, Stanford, CA, USA.
  • 30 Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala, Sweden; Department of Microbiology, New York University School of Medicine, New York, NY, USA.
  • 31 Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 32 Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 33 Perlmutter Cancer Center, New York University Langone Health, New York, NY, USA.
  • 34 Perlmutter Cancer Center, New York University Langone Health, New York, NY, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 35 Breast Unit, Champalimaud Clinical Center/Champalimaud Foundation, Lisbon, Portugal.
  • 36 Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 37 Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 38 Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
  • 39 Public Health Sciences Division/Translational Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • 40 Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • 41 Department of Pathology, University of California San Diego, La Jolla, CA, USA.
  • 42 Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
  • 43 Orthopedic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 44 Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA.
  • 45 Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA; Drukier Institute for Children's Health, Weill Cornell Medicine, New York, NY, USA.
  • 46 Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
  • 47 Division of Gastroenterology & Hepatology, Weill Cornell Medicine, New York, NY, USA.
  • 48 Thoracic Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 49 Department of Pathology and Laboratory Medicine, University of Vermont, Burlington, VT, USA.
  • 50 Department of Pediatrics and Biochemistry and Molecular Medicine, University of Southern California, CA, USA.
  • 51 Department of Population Sciences, Beckman Research Institute at City of Hope, Duarte, CA, USA.
  • 52 Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
  • 53 Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
  • 54 Champalimaud Research, Champalimaud Foundation, Lisbon, Portugal.
  • 55 Microenvironment and Metastasis Laboratory, Department of Molecular Oncology, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
  • 56 Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • 57 Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: jarnagiw@mskcc.org.
  • 58 Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. Electronic address: dcl2001@med.cornell.edu.
PMID: 32795414 DOI: 10.1016/j.cell.2020.07.009
Abstract

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.

Keywords

biomarkers; cancer; cancer of unknown primary origin; damage-associated molecular patterns; early cancer detection; exomeres; exosomes; extracellular vesicles and particles; liquid biopsy; proteomics.

Figures
Products