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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.

SUBMITTER: Hoshino A 

PROVIDER: S-EPMC7522766 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers.

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

Cell 20200813 4


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)  ...[more]

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