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细胞外囊泡和颗粒生物标志物可定义多种人类癌症
作者:小柯机器人 发布时间:2020/8/16 22:05:18

美国康奈尔医学院David Lyden等研究人员合作发现,细胞外囊泡和颗粒生物标志物可定义多种人类癌症。该研究于2020年8月13日在线发表于《细胞》。

研究人员调查了来自组织外植体(TE)、血浆和其他体液的426个人类样品中细胞外囊泡和颗粒(EVP)的蛋白质组学特征。在传统的外泌体标记中,CD9、HSPA8、ALIX和HSP90AB1代表pan-EVP标记,而ACTB、MSN和RAP1B是新颖的pan-EVP标记。
 
为了确认EVP是理想的诊断工具,研究人员分析了TE(n=151)和血浆来源(n=120)EVP的蛋白质组。TE EVP的比较可鉴定出以90%的敏感性、 94%的特异性将肿瘤与正常组织区分开的蛋白质(例如VCAN、TNC和THBS2)。血浆来源的EVP货物(包括免疫球蛋白)的机器学习分类显示,在检测癌症时灵敏度为95%、特异性为90%。
 
最后,研究人员在TE和血浆中定义了一组肿瘤类型特异性EVP蛋白,可以对未知原发性肿瘤进行分类。因此,EVP蛋白可以用作癌症检测并确定癌症类型的可靠生物标记。
 
据悉,对于用来癌症检测的组织和液体活检工具,临床需求尚未被满足。
 
附:英文原文

Title: Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers

Author: Ayuko Hoshino, Han Sang Kim, Linda Bojmar, Kofi Ennu Gyan, Michele Cioffi, Jonathan Hernandez, Constantinos P. Zambirinis, Gonalo Rodrigues, Henrik Molina, Sren Heissel, Milica Tesic Mark, Loc Steiner, Alberto Benito-Martin, Serena Lucotti, Angela Di Giannatale, Katharine Offer, Miho Nakajima, Caitlin Williams, Laura Nogués, Fanny A. Pelissier Vatter, Ayako Hashimoto, Alexander E. Davies, Daniela Freitas, Candia M. Kenific, Yonathan Ararso, Weston Buehring, Pernille Lauritzen, Yusuke Ogitani, Kei Sugiura, Naoko Takahashi, Maa Alekovi, Kayleen A. Bailey, Joshua S. Jolissant, Huajuan Wang, Ashton Harris, L. Miles Schaeffer, Guillermo García-Santos, Zoe Posner, Vinod P. Balachandran, Yasmin Khakoo, G. Praveen Raju, Avigdor Scherz, Irit Sagi, Ruth Scherz-Shouval, Yosef Yarden, Moshe Oren, Mahathi Malladi, Mary Petriccione, Kevin C. De Braganca, Maria Donzelli, Cheryl Fischer, Stephanie Vitolano, Geraldine P. Wright, Lee Ganshaw, Mariel Marrano, Amina Ahmed, Joe DeStefano, Enrico Danzer, Michael H.A. Roehrl, Norman J. Lacayo, Theresa C. Vincent, Martin R. Weiser, Mary S. Brady

Issue&Volume: 2020-08-13

Abstract: There is an unmet clinical need for improved tissue and liquid biopsy tools for cancerdetection. 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-EVPmarkers, while ACTB, MSN, and RAP1B are novel pan-EVP markers. To confirm that EVPsare 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 defineda panel of tumor-type-specific EVP proteins in TEs and plasma, which can classifytumors of unknown primary origin. Thus, EVP proteins can serve as reliable biomarkersfor cancer detection and determining cancer type.

DOI: 10.1016/j.cell.2020.07.009

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30874-6

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/