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.
Highlights
Malignant gliomas account for 78% of malignant primary brain tumors and include astrocytoma (AS) and oligodendroglioma (ODG), the oncogenic derivatives of the astrocytic and oligodendroglial lineages, respectively
We have used a multiplexed aptamer-based SOMAscan® 1.3K proteomic assay with simultaneous relative quantification of >1000 protein analytes for proteomic profiling of 89 patient-derived GBM, AS, and ODG malignant glioma cells
We analyzed 54 glioblastoma (GBM), 13 anaplastic astrocytoma (AS), and 21 oligodendroglioma (ODG) cell isolates cultured in DME/F12 containing 10%
Summary
Malignant gliomas account for 78% of malignant primary brain tumors and include astrocytoma (AS) and oligodendroglioma (ODG), the oncogenic derivatives of the astrocytic and oligodendroglial lineages, respectively. AS constitute the largest population of malignant gliomas (>63%) and include highly proliferative and invasive anaplastic astrocytoma (grade III) and glioblastoma multiforme (grade IV; GBM). ODG account for 2–4% of all primary brain tumors and have a better prognosis than most other malignant gliomas. GBM is a rare tumor with an annual incidence of 5 to 8 per 100,000 of population but constitutes about 60% of all primary human brain tumors [1]. Combined chemo-radiation treatment increases the median overall survival to about 14.6 months from 12.1 months with radiotherapy alone [6]. Current treatment options for malignant glioma remain limited and few patients achieve longer than 3-year survival [8]
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