Systematic review of protein biomarkers of invasive behavior in glioblastoma

Glioblastoma (GBM) is an aggressive and incurable brain tumor with a grave prognosis. Recurrence is inevitable even with maximal surgical resection, in large part because GBM is a highly invasive tumor. Invasiveness also contributes to the failure of multiple cornerstones of GBM therapy, including radiotherapy, temozolomide chemotherapy, and vascular endothelial growth factor blockade. In recent years there has been significant progress in the identification of protein biomarkers of invasive phenotype in GBM. In this article, we comprehensively review the literature and survey a broad spectrum of biomarkers, including proteolytic enzymes, extracellular matrix proteins, cell adhesion molecules, neurodevelopmental factors, cell signaling and transcription factors, angiogenic effectors, metabolic proteins, membrane channels, and cytokines and chemokines. In light of the marked variation seen in outcomes in GBM patients, the systematic use of these biomarkers could be used to form a framework for better prediction, prognostication, and treatment selection, as well as the identification of molecular targets for further laboratory investigation and development of nascent, directed therapies.