Publication:
Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers.

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dc.contributor.authorHoshino, Ayuko
dc.contributor.authorKim, Han Sang
dc.contributor.authorBojmar, Linda
dc.contributor.authorGyan, Kofi Ennu
dc.contributor.authorCioffi, Michele
dc.contributor.authorHernandez, Jonathan
dc.contributor.authorZambirinis, Constantinos P
dc.contributor.authorRodrigues, Gonçalo
dc.contributor.authorMolina, Henrik
dc.contributor.authorHeissel, Søren
dc.contributor.authorMark, Milica Tesic
dc.contributor.authorSteiner, Loïc
dc.contributor.authorBenito-Martin, Alberto
dc.contributor.authorLucotti, Serena
dc.contributor.authorDi Giannatale, Angela
dc.contributor.authorOffer, Katharine
dc.contributor.authorNakajima, Miho
dc.contributor.authorWilliams, Caitlin
dc.contributor.authorNogués, Laura
dc.contributor.authorPelissier Vatter, Fanny A
dc.contributor.authorHashimoto, Ayako
dc.contributor.authorDavies, Alexander E
dc.contributor.authorFreitas, Daniela
dc.contributor.authorKenific, Candia M
dc.contributor.authorArarso, Yonathan
dc.contributor.authorBuehring, Weston
dc.contributor.authorLauritzen, Pernille
dc.contributor.authorOgitani, Yusuke
dc.contributor.authorSugiura, Kei
dc.contributor.authorTakahashi, Naoko
dc.contributor.authorAlečković, Maša
dc.contributor.authorBailey, Kayleen A
dc.contributor.authorJolissant, Joshua S
dc.contributor.authorWang, Huajuan
dc.contributor.authorHarris, Ashton
dc.contributor.authorSchaeffer, L Miles
dc.contributor.authorGarcía-Santos, Guillermo
dc.contributor.authorPosner, Zoe
dc.contributor.authorBalachandran, Vinod P
dc.contributor.authorKhakoo, Yasmin
dc.contributor.authorRaju, G Praveen
dc.contributor.authorScherz, Avigdor
dc.contributor.authorSagi, Irit
dc.contributor.authorScherz-Shouval, Ruth
dc.contributor.authorYarden, Yosef
dc.contributor.authorOren, Moshe
dc.contributor.authorMalladi, Mahathi
dc.contributor.authorPetriccione, Mary
dc.contributor.authorDe Braganca, Kevin C
dc.contributor.authorDonzelli, Maria
dc.contributor.authorFischer, Cheryl
dc.contributor.authorVitolano, Stephanie
dc.contributor.authorWright, Geraldine P
dc.contributor.authorGanshaw, Lee
dc.contributor.authorMarrano, Mariel
dc.contributor.authorAhmed, Amina
dc.contributor.authorDeStefano, Joe
dc.contributor.authorDanzer, Enrico
dc.contributor.authorRoehrl, Michael H A
dc.contributor.authorLacayo, Norman J
dc.contributor.authorVincent, Theresa C
dc.contributor.authorWeiser, Martin R
dc.contributor.authorBrady, Mary S
dc.contributor.authorMeyers, Paul A
dc.contributor.authorWexler, Leonard H
dc.contributor.authorAmbati, Srikanth R
dc.contributor.authorChou, Alexander J
dc.contributor.authorSlotkin, Emily K
dc.contributor.authorModak, Shakeel
dc.contributor.authorRoberts, Stephen S
dc.contributor.authorBasu, Ellen M
dc.contributor.authorDiolaiti, Daniel
dc.contributor.authorKrantz, Benjamin A
dc.contributor.authorCardoso, Fatima
dc.contributor.authorSimpson, Amber L
dc.contributor.authorBerger, Michael
dc.contributor.authorRudin, Charles M
dc.contributor.authorSimeone, Diane M
dc.contributor.authorJain, Maneesh
dc.contributor.authorGhajar, Cyrus M
dc.contributor.authorBatra, Surinder K
dc.contributor.authorStanger, Ben Z
dc.contributor.authorBui, Jack
dc.contributor.authorBrown, Kristy A
dc.contributor.authorRajasekhar, Vinagolu K
dc.contributor.authorHealey, John H
dc.contributor.authorde Sousa, Maria
dc.contributor.authorKramer, Kim
dc.contributor.authorSheth, Sujit
dc.contributor.authorBaisch, Jeanine
dc.contributor.authorPascual, Virginia
dc.contributor.authorHeaton, Todd E
dc.contributor.authorLa Quaglia, Michael P
dc.contributor.authorPisapia, David J
dc.contributor.authorSchwartz, Robert
dc.contributor.authorZhang, Haiying
dc.contributor.authorLiu, Yuan
dc.contributor.authorShukla, Arti
dc.contributor.authorBlavier, Laurence
dc.contributor.authorDeClerck, Yves A
dc.contributor.authorLaBarge, Mark
dc.contributor.authorBissell, Mina J
dc.contributor.authorCaffrey, Thomas C
dc.contributor.authorGrandgenett, Paul M
dc.contributor.authorHollingsworth, Michael A
dc.contributor.authorBromberg, Jacqueline
dc.contributor.authorCosta-Silva, Bruno
dc.contributor.authorPeinado Selgas, Hector
dc.contributor.authorKang, Yibin
dc.contributor.authorGarcia, Benjamin A
dc.contributor.authorO'Reilly, Eileen M
dc.contributor.authorKelsen, David
dc.contributor.authorTrippett, Tanya M
dc.contributor.authorJones, David R
dc.contributor.authorMatei, Irina R
dc.contributor.authorJarnagin, William R
dc.contributor.authorLyden, David
dc.contributor.funderUnited States Department of Health & Human Services National Institutes of Health (NIH) - USA
dc.contributor.funderMelanoma Research Alliance
dc.contributor.funderHartwell Foundation
dc.contributor.funderThompson Family Foundation
dc.contributor.funderSTARR Consortium
dc.contributor.funderPediatric Oncology Experimental Therapeutics Investigator's Consortium
dc.contributor.funderAlex's Lemonade Stand Foundation
dc.contributor.funderBreast Cancer Research Foundation
dc.contributor.funderACEV Foundation
dc.contributor.funderSusan G. Komen Breast Cancer Foundation
dc.contributor.funderNational Research Foundation of Korea
dc.contributor.funderSeverance Hospital Research fund for Clinical Excellence
dc.contributor.funderYonsei University College of Medicine
dc.contributor.funderWeill Cornell Medical College Clinical and Translational Science Center - NIH/NCATS
dc.date.accessioned2025-01-07T17:21:42Z
dc.date.available2025-01-07T17:21:42Z
dc.date.issued2020-08-20
dc.description.abstractThere 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.
dc.description.peerreviewedNo
dc.description.tableofcontentsThis work is dedicated to Maria de Sousa, Emeritus Professor at the University of Porto, Adjunct Professor in Pediatrics at Weill Cornell Medicine, and co-founder of the prestigious "Graduate Program in Basic and Applied Biology (GABBA)'' at the University of Porto, who succumbed to COVID-19 on April 14, 2020. Maria was a noted immunologist who pioneered studies in lymphocyte migration, defining the concept of "ecotaxis.'' We honor her last wish: "In your living the hope of my lasting.'' We thank the Mesothelioma Research Bank (CDC NIOSH 1-U19-OH009077-01 NMVP) for plasma samples, Medical Illustration & Design Services of Yonsei University College of Medicine for the art, and the Electron Microscopy & Histology services of the Weill Cornell Medicine Microscopy & Image Analysis Core for TEM with NIH Shared Instrumentation Grant (S10RR027699). The authors gratefully acknowledge support from the National Cancer Institute (CA224175 to D.L. and V.P.B., CA210240 to D.L. and M.H., CA232093 to D.L., CA163117 and CA207983 to D.L. and Y.D.C., CA163120 to D.L. and S.K.B., CA169416 to D.L. and H.P., CA169538 to D.L. and M.J.B., CA218513 to D.L. and H.Z., and AI144301 to D.L. and V.P.), the United States Department of Defense (W81XWH-13-1-0425 to D.L. and Y.K., W81XWH-13-1-0427 and W81XWH-13-1-0249 to D.L., and W81XWH-14-1-0199 to D.L. and A.S., the Melanoma Research Alliance (to H.P), the Hartwell Foundation (to D.L. and J.B.), the Thompson Family Foundation (to D.K., A.S., D.L., R.S., Y.Y., I.S., R.S.S., V.P.B., and E.O.), the STARR Consortium (I9-A9-056 to D.L., P.R., K.K., and H.Z. and I8-A8-123 to D.L. and H.P.), the Pediatric Oncology Experimental Therapeutics Investigator's Consortium (to T.T., D.L., M.H.R., M.B., M.P.L., T.H., and S.A.), Alex's Lemonade Stand Foundation (to D.L. and P.R.), the Breast Cancer Research Foundation (to D.L., M.J.B., and C.M.G.), the Feldstein Medical Foundation (to D.L. and H.P.), the Tortolani Foundation (to D.L. and J.B.), the Clinical & Translational Science Center (to D.L. and H.Z.), the Mary Kay Ash Charitable Foundation (to D.L. and I.M.), the Malcolm Hewitt Weiner Foundation, the Manning Foundation, the Daniel P. and Nancy C. Paduano Family Foundation, the James Paduano Foundation, the Sohn Foundation, the AHEPA Vth District Cancer Research Foundation, the Daedalus Fund, Selma and Lawrence Ruben Science to Industry Bridge Award, the Children's Cancer and Blood Foundation (to D.L.), the Scott and Lisa Stuart Family Foundation, the D10 Foundation (to T.T.), Susan G. Komen Postdoctoral Fellowship (PDF15331556, JST PRESTO 30021, and JSPS KAKENHI JP19K23743 to A.H.), the National Research Foundation of Korea (2019R1C1C1006709 and 2018R1A5A2025079 [MSIT]), Severance Hospital Research fund for Clinical Excellence (C-2019-0026), faculty research grant of Yonsei University College of Medicine (6-2019-0090), Daewoong Foundation Research Grant (to H.S.K.), the Swedish Cancer Society Pancreatic Cancer Fellowship (to L.B.), the Lions International Postdoctoral fellowship (to L.B.), the Sweden-America stipend (to L.B.), the Memorial Sloan Kettering Cancer Center Metastasis and Tumor Ecosystems Center fellowship (to C.P.Z.), the Weill Cornell Medical College Clinical and Translational Science Center funded by NIH/NCATS (UL1TR002384 to J.S.J.), the "Little Eric Foundation'' (to Y.K.), and the EVAN Foundation (to K.K.).
dc.format.number4
dc.format.page1044-1061
dc.format.volume182
dc.identifier.citationCell . 2020 Aug 20;182(4):1044-1061
dc.identifier.journalCell
dc.identifier.pmchttps://pmc.ncbi.nlm.nih.gov/articles/PMC7522766/pdf/nihms-1612511.pdf
dc.identifier.pubmedID32795414
dc.identifier.urihttps://hdl.handle.net/20.500.12105/25959
dc.language.isoeng
dc.publisherCell Press
dc.relation.publisherversionhttp://10.1016/j.cell.2020.07.009
dc.repisalud.institucionCNIO
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Microambiente y Metástasis
dc.rights.accessRightsopen access
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectbiomarkers
dc.subjectcancer
dc.subjectcancer of unknown primary origin
dc.subjectdamage-associated molecular patterns
dc.subjectearly cancer detection
dc.subjectexomeres
dc.subjectexosomes
dc.subjectextracellular vesicles and particles
dc.subjectliquid biopsy
dc.subjectproteomics
dc.titleExtracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers.
dc.typeresearch article
dc.type.hasVersionAM
dspace.entity.typePublication
relation.isAuthorOfPublicationf33d0f5a-ce2e-4874-a2d8-03c0974e8b1d
relation.isAuthorOfPublication.latestForDiscoveryf33d0f5a-ce2e-4874-a2d8-03c0974e8b1d

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