Slow Off-Rate Modified Aptamer (SOMAmer) Proteomic Analysis of Patient-Derived Malignant Glioma Identifies Distinct Cellular Proteomes

慢解离率修饰适体 (SOMAmer) 对患者来源的恶性胶质瘤进行蛋白质组学分析,鉴定出不同的细胞蛋白质组

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作者:Thatchawan Thanasupawat, Aleksandra Glogowska, Christopher Pascoe, Sai Nivedita Krishnan, Maliha Munir, Farhana Begum, Jason Beiko, Jerry Krcek, Marc R Del Bigio, Marshall Pitz, Yaoqing Shen, Victor Spicer, Kevin M Coombs, John Wilkins, Sabine Hombach-Klonisch, Thomas Klonisch

Abstract

Malignant gliomas derive from brain glial cells and represent >75% of primary brain tumors. This includes anaplastic astrocytoma (grade III; AS), the most common and fatal glioblastoma multiforme (grade IV; GBM), and oligodendroglioma (ODG). We have generated patient-derived AS, GBM, and ODG cell models to study disease mechanisms and test patient-centered therapeutic strategies. We have used an aptamer-based high-throughput SOMAscan® 1.3K assay to determine the proteomic profiles of 1307 different analytes. SOMAscan® proteomes of AS and GBM self-organized into closely adjacent proteomes which were clearly distinct from ODG proteomes. GBM self-organized into four proteomic clusters of which SOMAscan® cluster 4 proteome predicted a highly inter-connected proteomic network. Several up- and down-regulated proteins relevant to glioma were successfully validated in GBM cell isolates across different SOMAscan® clusters and in corresponding GBM tissues. Slow off-rate modified aptamer proteomics is an attractive analytical tool for rapid proteomic stratification of different malignant gliomas and identified cluster-specific SOMAscan® signatures and functionalities in patient GBM cells.

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