Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers.

TitleExtracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers.
Publication TypeJournal Article
Year of Publication2020
AuthorsHoshino, A, Kim, HSang, Bojmar, L, Gyan, KEnnu, Cioffi, M, Hernandez, J, Zambirinis, CP, Rodrigues, G, Molina, H, Heissel, S, Mark, MTesic, Steiner, L, Benito-Martin, A, Lucotti, S, Di Giannatale, A, Offer, K, Nakajima, M, Williams, C, Nogués, L, Vatter, FAPelissie, Hashimoto, A, Davies, AE, Freitas, D, Kenific, CM, Ararso, Y, Buehring, W, Lauritzen, P, Ogitani, Y, Sugiura, K, Takahashi, N, Alečković, M, Bailey, KA, Jolissant, JS, Wang, H, Harris, A, L Schaeffer, M, García-Santos, G, Posner, Z, Balachandran, VP, Khakoo, Y, G Raju, P, Scherz, A, Sagi, I, Scherz-Shouval, R, Yarden, Y, Oren, M, Malladi, M, Petriccione, M, De Braganca, KC, Donzelli, M, Fischer, C, Vitolano, S, Wright, GP, Ganshaw, L, Marrano, M, Ahmed, A, DeStefano, J, Danzer, E, Roehrl, MHA, Lacayo, NJ, Vincent, TC, Weiser, MR, Brady, MS, Meyers, PA, Wexler, LH, Ambati, SR, Chou, AJ, Slotkin, EK, Modak, S, Roberts, SS, Basu, EM, Diolaiti, D, Krantz, BA, Cardoso, F, Simpson, AL, Berger, M, Rudin, CM, Simeone, DM, Jain, M, Ghajar, CM, Batra, SK, Stanger, BZ, Bui, J, Brown, KA, Rajasekhar, VK, Healey, JH, de Sousa, M, Kramer, K, Sheth, S, Baisch, J, Pascual, V, Heaton, TE, La Quaglia, MP, Pisapia, DJ, Schwartz, R, Zhang, H, Liu, Y, Shukla, A, Blavier, L, DeClerck, YA, LaBarge, M, Bissell, MJ, Caffrey, TC, Grandgenett, PM, Hollingsworth, MA, Bromberg, J, Costa-Silva, B, Peinado, H, Kang, Y, Garcia, BA, O'Reilly, EM, Kelsen, D, Trippett, TM, Jones, DR, Matei, IR, Jarnagin, WR, Lyden, D
Date Published2020 Aug 20
KeywordsAnimals, 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

<p>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.</p>

Alternate JournalCell
PubMed ID32795414
PubMed Central IDPMC7522766
Grant ListU54 CA163120 / CA / NCI NIH HHS / United States
U54 CA163117 / CA / NCI NIH HHS / United States
R01 CA218513 / CA / NCI NIH HHS / United States
U19 OH009077 / OH / NIOSH CDC HHS / United States
U19 AI144301 / AI / NIAID NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
UL1 TR002384 / TR / NCATS NIH HHS / United States
U01 CA210240 / CA / NCI NIH HHS / United States
R01 CA064786 / CA / NCI NIH HHS / United States
R01 CA207983 / CA / NCI NIH HHS / United States
P50 CA127297 / CA / NCI NIH HHS / United States
R50 CA211462 / CA / NCI NIH HHS / United States
S10 RR027699 / RR / NCRR NIH HHS / United States
R01 CA169416 / CA / NCI NIH HHS / United States
U01 CA169538 / CA / NCI NIH HHS / United States
U01 CA224175 / CA / NCI NIH HHS / United States
R01 CA217169 / CA / NCI NIH HHS / United States
R35 CA232093 / CA / NCI NIH HHS / United States