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

Int J Mol Sci. 2021 Sep 3;22(17):9566. doi: 10.3390/ijms22179566.

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: SOMAmers; glioblastoma; glioma; patient cell isolates; proteomic clusters.

MeSH terms

  • Aptamers, Nucleotide / chemistry*
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • Neoplasm Proteins / metabolism*
  • Proteome / metabolism*
  • Proteomics*
  • Tumor Cells, Cultured

Substances

  • Aptamers, Nucleotide
  • Neoplasm Proteins
  • Proteome