@article{186276, keywords = {Animals, Humans, proteomics, Cell Line, Mice, Mice, Inbred C57BL, Proteome, Sensitivity and Specificity, Neoplasms, Microfilament Proteins, machine learning, Biomarkers, Tumor, rap GTP-Binding Proteins, Extracellular Vesicles, HSC70 Heat-Shock Proteins, Tetraspanin 29}, author = {Ayuko Hoshino and Han Sang Kim and Linda Bojmar and Kofi Ennu Gyan and Michele Cioffi and Jonathan Hernandez and Constantinos Zambirinis and Gon{\c c}alo Rodrigues and Henrik Molina and S{\o}ren Heissel and Milica Tesic Mark and Lo{\"\i}c Steiner and Alberto Benito-Martin and Serena Lucotti and Angela Di Giannatale and Katharine Offer and Miho Nakajima and Caitlin Williams and Laura Nogu{\'e}s and Fanny Pelissier Vatter and Ayako Hashimoto and Alexander Davies and Daniela Freitas and Candia Kenific and Yonathan Ararso and Weston Buehring and Pernille Lauritzen and Yusuke Ogitani and Kei Sugiura and Naoko Takahashi and Ma{\v s}a Ale{\v c}kovi{\'c} and Kayleen Bailey and Joshua Jolissant and Huajuan Wang and Ashton Harris and Miles Schaeffer and Guillermo Garc{\'\i}a-Santos and Zoe Posner and Vinod Balachandran and Yasmin Khakoo and Praveen Raju and Avigdor Scherz and Irit Sagi and Ruth Scherz-Shouval and Yosef Yarden and Moshe Oren and Mahathi Malladi and Mary Petriccione and Kevin De Braganca and Maria Donzelli and Cheryl Fischer and Stephanie Vitolano and Geraldine Wright and Lee Ganshaw and Mariel Marrano and Amina Ahmed and Joe DeStefano and Enrico Danzer and Michael Roehrl and Norman Lacayo and Theresa Vincent and Martin Weiser and Mary Brady and Paul Meyers and Leonard Wexler and Srikanth Ambati and Alexander Chou and Emily Slotkin and Shakeel Modak and Stephen Roberts and Ellen Basu and Daniel Diolaiti and Benjamin Krantz and Fatima Cardoso and Amber Simpson and Michael Berger and Charles Rudin and Diane Simeone and Maneesh Jain and Cyrus Ghajar and Surinder Batra and Ben Stanger and Jack Bui and Kristy Brown and Vinagolu Rajasekhar and John Healey and de Maria Sousa and Kim Kramer and Sujit Sheth and Jeanine Baisch and Virginia Pascual and Todd Heaton and Michael La Quaglia and David Pisapia and Robert Schwartz and Haiying Zhang and Yuan Liu and Arti Shukla and Laurence Blavier and Yves DeClerck and Mark LaBarge and Mina Bissell and Thomas Caffrey and Paul Grandgenett and Michael Hollingsworth and Jacqueline Bromberg and Bruno Costa-Silva and Hector Peinado and Yibin Kang and Benjamin Garcia and Eileen O{\textquoteright}Reilly and David Kelsen and Tanya Trippett and David Jones and Irina Matei and William Jarnagin and David Lyden}, title = {Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers}, 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.
}, year = {2020}, journal = {Cell}, volume = {182}, pages = {1044-1061.e18}, month = {08/2020}, issn = {1097-4172}, doi = {10.1016/j.cell.2020.07.009}, language = {eng}, }