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人胶质母细胞瘤和髓母细胞瘤细胞外基质蛋白质组重塑。

Extracellular Matrix Proteome Remodeling in Human Glioblastoma and Medulloblastoma.

机构信息

Cellular and Molecular Biology Laboratory (LIM 15), Neurology Department, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Sao Paulo 01246-903, Brazil.

Faculty of Science and Engineering, Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, Groningen 9713 AV, The Netherlands.

出版信息

J Proteome Res. 2021 Oct 1;20(10):4693-4707. doi: 10.1021/acs.jproteome.1c00251. Epub 2021 Sep 17.

Abstract

Medulloblastomas (MBs) and glioblastomas (GBMs) are high-incidence central nervous system tumors. Different origin sites and changes in the tissue microenvironment have been associated with the onset and progression. Here, we describe differences between the extracellular matrix (ECM) signatures of these tumors. We compared the proteomic profiles of MB and GBM decellularized tumor samples between each other and their normal decellularized brain site counterparts. Our analysis revealed that 19, 28, and 11 ECM proteins were differentially expressed in MBs, GBMs, and in both MBs and GBMs, respectively. Next, we validated key findings by using a protein tissue array with 53 MB and 55 GBM cases and evaluated the clinical relevance of the identified differentially expressed proteins through their analysis on publicly available datasets, 763 MB samples from the GSE50161 and GSE85217 studies, and 115 GBM samples from RNAseq-TCGA. We report a shift toward a denser fibrillary ECM as well as a clear alteration in the glycoprotein signature, which influences the tumor pathophysiology. MS data have been submitted to the PRIDE repository, project accession: PXD023350.

摘要

髓母细胞瘤(MBs)和胶质母细胞瘤(GBMs)是高发的中枢神经系统肿瘤。不同的起源部位和组织微环境的变化与发病和进展有关。在这里,我们描述了这些肿瘤细胞外基质(ECM)特征的差异。我们比较了彼此的 MB 和 GBM 去细胞化肿瘤样本以及其正常去细胞化脑区对应的蛋白质组学图谱。我们的分析表明,19、28 和 11 种 ECM 蛋白在 MB、GBM 以及 MB 和 GBM 中分别存在差异表达。接下来,我们使用包含 53 例 MB 和 55 例 GBM 病例的蛋白质组织阵列对关键发现进行了验证,并通过对来自 GSE50161 和 GSE85217 研究的 763 例 MB 样本和来自 RNAseq-TCGA 的 115 例 GBM 样本的公共数据集分析评估了鉴定的差异表达蛋白的临床相关性。我们报告了 ECM 向更密集的纤维状以及糖蛋白特征明显改变的转变,这影响了肿瘤的病理生理学。MS 数据已提交到 PRIDE 存储库,项目访问号:PXD023350。

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