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Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers

Authors
Ayuko Hoshino,Han Kim
Linda Bojmar,Kofi Gyan,Michele Cioffi,Jonathan Hernandez,Constantinos Zambirinis,Gonçalo Rodrigues,Henrik Molina,Søren Heissel,Milica Mark,Loïc Steiner,Alberto Benito‐Martín,Serena Lucotti,Angela Giannatale,Katharine Offer,Miho Nakajima,Caitlin Williams,Laura Nogués,Fanny Pelissier,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 Jolissaint,Huajuan Wang,Ashton Harris,Laurent Schaeffer,Guillermo García‐Santos,Zoe Posner,Vinod Balachandran,Yasmin Khakoo,G. Raju,Avigdor Scherz,Irit Sagi,Ruth Scherz‐Shouval,Yosef Yarden,Moshe Oren,Mahathi Malladi,Mary Petriccione,Kevin 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,Fátima 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 Sousa,Kim Krämer,Sujit Sheth,Jeanine Baisch,Virginia Pascual,Todd Heaton,Michael LaQuaglia,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 García,Eileen O’Reilly,David Kelsen,Tanya Trippett,David Jones,Irina Matei,William Jarnagin,David Lyden,Michèle Cioffi
+116 authors
,Alberto Benito‐Martin
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Published
Aug 1, 2020
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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.

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