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文章:

人类脑肿瘤囊液连续样本的蛋白质组学分析

Proteomic Analysis on Sequential Samples of Cystic Fluid Obtained from Human Brain Tumors

原文发布日期:11 August 2023

DOI: 10.3390/cancers15164070

类型: Article

开放获取: 是

 

英文摘要:

Cystic formation in human primary brain tumors is a relatively rare event whose incidence varies widely according to the histotype of the tumor. Composition of the cystic fluid has mostly been characterized in samples collected at the time of tumor resection and no indications of the evolution of cystic content are available. We characterized the evolution of the proteome of cystic fluid using a bottom-up proteomic approach on sequential samples obtained from secretory meningioma (SM), cystic schwannoma (CS) and cystic high-grade glioma (CG). We identified 1008 different proteins; 74 of these proteins were found at least once in the cystic fluid of all tumors. The most abundant proteins common to all tumors studied derived from plasma, with the exception of prostaglandin D2 synthase, which is a marker of cerebrospinal fluid origin. Overall, the protein composition of cystic fluid obtained at different times from the same tumor remained stable. After the identification of differentially expressed proteins (DEPs) and the protein–protein interaction network analysis, we identified the presence of tumor-specific pathways that may help to characterize tumor–host interactions. Our results suggest that plasma proteins leaking from local blood–brain barrier disruption are important contributors to cyst fluid formation, but cerebrospinal fluid (CSF) and the tumor itself also contribute to the cystic fluid proteome and, in some cases, as with immunoglobulin G, shows tumor-specific variations that cannot be simply explained by differences in vessel permeability or blood contamination.

 

摘要翻译: 

人类原发性脑肿瘤中的囊性形成是一种相对罕见的现象,其发生率因肿瘤组织类型而异。目前对囊液成分的研究主要基于肿瘤切除时采集的样本,尚无关于囊液成分演变过程的明确数据。本研究采用自下而上的蛋白质组学方法,对分泌性脑膜瘤、囊性神经鞘瘤及囊性高级别胶质瘤的连续样本进行分析,系统描绘了囊液蛋白质组的动态演变特征。共鉴定出1008种不同蛋白质,其中74种蛋白质在所有肿瘤囊液中至少出现一次。除作为脑脊液标志物的前列腺素D2合酶外,所有肿瘤囊液中最丰富的共有蛋白均来源于血浆。总体而言,同一肿瘤不同时间点获取的囊液蛋白质组成保持稳定。通过差异表达蛋白质鉴定及蛋白质相互作用网络分析,我们发现了可能表征肿瘤-宿主相互作用的肿瘤特异性通路。研究结果表明,局部血脑屏障破坏导致的血浆蛋白渗漏是囊液形成的重要因素,但脑脊液及肿瘤本身也对囊液蛋白质组构成贡献。在某些情况下(如免疫球蛋白G),囊液成分呈现肿瘤特异性变化,这种变化无法单纯用血管通透性差异或血液污染来解释。

 

原文链接:

Proteomic Analysis on Sequential Samples of Cystic Fluid Obtained from Human Brain Tumors

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