Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers

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• Alternative Title:
  Cell
• Personal Author:
  Hoshino, Ayuko ; Kim, Han Sang ; Bojmar, Linda ; Gyan, Kofi Ennu ; Cioffi, Michele ; Hernandez, Jonathan ; Zambirinis, Constantinos P. ; Rodrigues, Gonçalo ; Molina, Henrik ; Heissel, Søren ; Mark, Milica Tesic ; Steiner, Loïc ; Benito-Martin, Alberto ; Lucotti, Serena ; Giannatale, Angela Di ; Offer, Katharine ; Nakajima, Miho ; Williams, Caitlin ; Nogués, Laura ; Vatter, Fanny A. Pelissier ; Hashimoto, Ayako ; Davies, Alexander E. ; Freitas, Daniela ; Kenific, Candia M. ; Ararso, Yonathan ; Buehring, Weston ; Lauritzen, Pernille ; Ogitani, Yusuke ; Sugiura, Kei ; Takahashi, Naoko ; Alečković, Maša ; Bailey, Kayleen A. ; Jolissaint, Joshua S. ; Wang, Huajuan ; Harris, Ashton ; Schaeffer, L. Miles ; García-Santos, Guillermo ; Posner, Zoe ; Balachandran, Vinod P. ; Khakoo, Yasmin ; Raju, G. Praveen ; Scherz, Avigdor ; Sagi, Irit ; Scherz-Shouval, Ruth ; Yarden, Yosef ; Oren, Moshe ; Malladi, Mahathi ; Petriccione, Mary ; De Braganca, Kevin C. ; Donzelli, Maria ; Fischer, Cheryl ; Vitolano, Stephanie ; Wright, Geraldine P. ; Ganshaw, Lee ; Marrano, Mariel ; Ahmed, Amina ; DeStefano, Joe ; Danzer, Enrico ; Roehrl, Michael H.A. ; Lacayo, Norman J. ; Vincent, C. Theresa ; Weiser, Martin R. ; Brady, Mary S. ; Meyers, Paul A. ; Wexler, Leonard H. ; Ambati, Srikanth R. ; Chou, Alexander J. ; Slotkin, Emily K. ; Modak, Shakeel ; Roberts, Stephen S. ; Basu, Ellen M. ; Diolaiti, Daniel ; Krantz, Benjamin A. ; Cardoso, Fatima ; Simpson, Amber L. ; Berger, Michael ; Rudin, Charles M. ; Simeone, Diane M. ; Jain, Maneesh ; Ghajar, Cyrus M. ; Batra, Surinder K. ; Stanger, Ben Z. ; Bui, Jack ; Brown, Kristy A. ; Rajasekhar, Vinagolu K. ; Healey, John H. ; de Sousa, Maria ; Kramer, Kim ; Sheth, Sujit ; Baisch, Jeanine ; Pascual, Virginia ; Heaton, Todd E. ; Quaglia, Michael P. La ; Pisapia, David J. ; Schwartz, Robert ; Zhang, Haiying ; Liu, Yuan ; Shukla, Arti ; Blavier, Laurence ; DeClerck, Yves A. ; LaBarge, Mark ; Bissell, Mina J. ; Caffrey, Thomas C. ; Grandgenett, Paul M. ; Hollingsworth, Michael A. ; Bromberg, Jacqueline ; Costa-Silva, Bruno ; Peinado, Hector ; Kang, Yibin ; Garcia, Benjamin A. ; O’Reilly, Eileen M. ; Kelsen, David ; Trippett, Tanya M. ; Jones, David R. ; Matei, Irina R. ; Jarnagin, William R. ; Lyden, David
• Description:
  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.
• Subjects:
  Animals Article Biomarkers, Tumor Cell Line Extracellular Vesicles HSC70 Heat-Shock Proteins Humans Machine Learning Mice Mice, Inbred C57BL Microfilament Proteins Neoplasms Proteome Proteomics Rap GTP-Binding Proteins Sensitivity And Specificity Tetraspanin 29

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• Source:
  Cell. 182(4):1044-1061.e18
• Pubmed ID:
  32795414
• Pubmed Central ID:
  PMC7522766
• Document Type:
  Journal Article
• Funding:
  U54 CA163120/CA/NCI NIH HHSUnited States/ ; U54 CA163117/CA/NCI NIH HHSUnited States/ ; R01 CA218513/CA/NCI NIH HHSUnited States/ ; U19 OH009077/OH/NIOSH CDC HHSUnited States/ ; U19 AI144301/AI/NIAID NIH HHSUnited States/ ; P30 CA008748/CA/NCI NIH HHSUnited States/ ; UL1 TR002384/TR/NCATS NIH HHSUnited States/ ; U01 CA210240/CA/NCI NIH HHSUnited States/ ; R01 CA207983/CA/NCI NIH HHSUnited States/ ; P50 CA127297/CA/NCI NIH HHSUnited States/ ; R50 CA211462/CA/NCI NIH HHSUnited States/ ; S10 RR027699/RR/NCRR NIH HHSUnited States/ ; R01 CA169416/CA/NCI NIH HHSUnited States/ ; U01 CA169538/CA/NCI NIH HHSUnited States/ ; U01 CA224175/CA/NCI NIH HHSUnited States/ ; R01 CA217169/CA/NCI NIH HHSUnited States/ ; R35 CA232093/CA/NCI NIH HHSUnited States/
• Volume:
  182
• Issue:
  4
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:33d838a60c3b4329a99858ff90d86f2503da74f037a4fc17e94d9f44083e059c
• Download URL:
  https://stacks.cdc.gov/view/cdc/94603/cdc_94603_DS1.pdf
• File Type:
  [PDF - 4.41 MB ]