Proteomics of Extracellular Vesicle in Glioblastoma

Abstract

Glioblastoma multiforme (GBM), a high-grade astrocytic brain tumor, has highly aggressive and hetero- geneous phenotypes with active cellular invasion, angiogenesis, and immune system modulation in the tumor microenvironment driven by complex oncogenic mutations. This abnormal disease progression could be attributed to extracellular vesicles (EVs) containing diverse bioactive molecules, including pro- teins, genetic materials, lipids, and metabolites. Importantly, GBM-related EVs have emerged as key mediators in cancer progression, acting as carriers for the transfer of oncogenic proteins such as epi- dermal growth factor receptor variant III (EGFRvIII) and genetic materials (DNA and RNA). Remarkably, recent progress in EV analysis has enabled its purification with high confidence by estimating the purity level of isolated EVs. Thus, mass spectrometry-based proteomic analysis could generate highly reliable vesicular proteomes. Glioblastoma EV proteome studies have revealed the specific increase in vesicu- lar protein cargo due to their oncogenic transformation, and these EV proteins are closely associated with cancer invasion. Moreover, their proteomic data reflects the molecular alterations that occur in pa- rental GBM and provides potent diagnostic information in a minimally invasive manner in liquid biopsy. Thus, proteomic analysis of GBM EVs could provide an increased understanding of their biological properties and activity in the GBM microenvironment, and provide significant implications for advanced approaches in the diagnosis of these intractable tumors