Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1044-1061.e18
JournalCell
Volume182
Issue number4
DOIs
StatePublished - Aug 20 2020

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Keywords

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

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    Hoshino, A., Kim, H. S., Bojmar, L., Gyan, K. E., Cioffi, M., Hernandez, J., Zambirinis, C. P., Rodrigues, G., Molina, H., Heissel, S., Mark, M. T., Steiner, L., Benito-Martin, A., Lucotti, S., Di Giannatale, A., Offer, K., Nakajima, M., Williams, C., Nogués, L., ... Lyden, D. (2020). Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers. Cell, 182(4), 1044-1061.e18. https://doi.org/10.1016/j.cell.2020.07.009