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Slow Off-Rate Modified Aptamer (SOMAmer) Proteomic Analysis of Patient-Derived Malignant Glioma Identifies Distinct Cellular Proteomes
Authors: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.
Keywords:glioma   glioblastoma   proteomic clusters   SOMAmers   patient cell isolates
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