Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers.

Author

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

Publication Year

2020

Type

Journal Article

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

Animals, Mice, Humans, Cell Line, Mice, Inbred C57BL, Proteomics, Proteome, Sensitivity and Specificity, Biomarkers, Tumor, Microfilament Proteins, Neoplasms, Extracellular Vesicles, Machine Learning, HSC70 Heat-Shock Proteins, Tetraspanin 29, rap GTP-Binding Proteins

Journal

Cell

Volume

182

Issue

Pages

1044-1061.e18

Date Published

2020 Aug 20

ISSN Number

1097-4172

DOI

10.1016/j.cell.2020.07.009

Alternate Journal

Cell

PMCID

PMC7522766

PMID

32795414