Glioblastoma: development of new diagnostic tools based on EV-associated proteins

Glioblastomas multiforme (GBM) are the most common malignant primary brain tumors in adults. They are highly aggressive and have an overall survival of <15 months despite maximal surgical resection and chemoradiation (Ostrom, 2019). GBMs are typically heterogeneous with a wide range of genetic and epigenetic variations among tumor cells. Extracellular vesicles (EVs) represent one of the plausible ways through which can be obtained a better understanding of the heterogeneous subpopulations of GBM / molecular signatures. EVs hold promise for the discovery of potential tumours biomarkers useful in clinical managment for GBM patient diagnosis and follow-up. Isolating EVs from body fluids and screening their protein content may serve as a complementary approach to assess the heterogeneous molecular landscape of GBM as tumors evolve. Many reports support the idea that Hsps are implicates in the pathogenesis and in the progression of different human neoplasms, by uncertain metabolic mechanism. Athough Hsps perform their canonical “chaperoning” functions in both prokariotic and eukaryotic cells, they have also acquired, probly during evolution, “extra-chaperoning” roles. Among these roles, there are some involved in the mechanism of cancerogenesis. In this study, we evaluate the exspression of some Hsps (in particular Hsp10, Hsp27, Hsp60, Hsp70, and Hsp90) through experiments of immnohistochemistry in samples of GBM and healthy controls, and also by immunofluorescence analysis on priamry and secondary cell lines of GBM. We also focused to research these proteins in EVs isolated from plasma obatained from patients with GBM, before and after surgery. The isolation was followed by a morphological and biochemical characterization of the EVs, in order to better study the characteristics of these potential natural carriers for the tool development for diagnostic and, possibly, also follow-up biopsy.