Circulating protein biomarkers of glioblastoma: methodologic approaches and perspectives of development

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor, characterized by an extremely poor prognosis. Difficulties in diagnostics and monitoring this disease stimulate the search for minimally invasive approaches. In this context liquid biopsy is considered as a promising approach. This review analyzes results of recent studies aimed at identifying circulating protein biomarkers of GBM in plasma and serum. These biomarkers include cell-free circulating plasma proteins and proteins of extracellular vesicles (EVs). Special attention is paid to the results obtained using both immunochemical methods and mass spectrometric approaches for identification of protein biomarkers, which have been summarized here as a list of identified potential diagnostic and prognostic biomarkers. Analysis of the literature demonstrates that proteomic analysis focused on the plasma EV fraction significantly expands the possibilities for identifying biomarkers for noninvasive GBM diagnostics and monitoring.