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健康和肿瘤人类结肠类器官的个性化蛋白质组谱揭示了结直肠癌的个体多样性和基本特征。

Personalized Proteome Profiles of Healthy and Tumor Human Colon Organoids Reveal Both Individual Diversity and Basic Features of Colorectal Cancer.

机构信息

Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 3584 Utrecht, the Netherlands; Netherlands Proteomics Center, Padualaan 8, 3584 Utrecht, the Netherlands.

Princess Maxima Center for Pediatric Oncology, Uppsalalaan 8, 3584 Utrecht, Netherlands.

出版信息

Cell Rep. 2017 Jan 3;18(1):263-274. doi: 10.1016/j.celrep.2016.12.016.

Abstract

Diseases at the molecular level are complex and patient dependent, necessitating development of strategies that enable precision treatment to optimize clinical outcomes. Organoid technology has recently been shown to have the potential to recapitulate the in vivo characteristics of the original individual's tissue in a three-dimensional in vitro culture system. Here, we present a quantitative mass-spectrometry-based proteomic analysis and a comparative transcriptomic analysis of human colorectal tumor and healthy organoids derived, in parallel, from seven patients. Although gene and protein signatures can be derived to distinguish the tumor organoid population from healthy organoids, our data clearly reveal that each patient possesses a distinct organoid signature at the proteomic level. We demonstrate that a personalized patient-specific organoid proteome profile can be related to the diagnosis of a patient and with future development contribute to the generation of personalized therapies.

摘要

在分子水平上,疾病是复杂的,且依赖于患者,这就需要制定策略,实现精准治疗,优化临床结果。类器官技术最近已经被证明具有在三维体外培养系统中重现原始个体组织体内特征的潜力。在这里,我们对来自七位患者的人结直肠肿瘤和健康类器官进行了基于定量质谱的蛋白质组学分析和比较转录组学分析。尽管可以得出基因和蛋白质特征来区分肿瘤类器官群体和健康类器官,但我们的数据清楚地表明,在蛋白质组水平上,每个患者都具有独特的类器官特征。我们证明,个性化的患者特异性类器官蛋白质组图谱可以与患者的诊断相关,并在未来的发展中有助于生成个性化治疗。

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