Comprehensive proteomic investigation of high-grade and low-grade gliomas reveals pathways associated with cancer metastasis and candidate protein markers of therapeutic potential

High grade gliomas (HGGs), are the most malignant and difficult to treat brain tumors. Despite several studies on glioma pathobiology there is no comparative proteomics study on high-grade and low-grade gliomas which uncovers the mechanism behind the aggressive mesenchymal behaviour of HGGs. In this study, tissue samples of high-grade and low-grade gliomas were processed for label free quantification (LFQ) using HR-LC MS/MS. The analysis identified 140 differentially expressed proteins, GSEA and protein-protein interaction analysis showed over expression of pathways like; ECM remodelling, Focal Adhesion, EMT and Glycan Biosynthesis in HGG. The key proteins were validated using multiple reaction monitoring experiment. ECM glycoproteins including; Fibronectin, Fibrinogens, Collagens, Vitronectin along with mesenchymal markers such as Vimentin and TGF-β came over-expressed in HGGs. The over-expression of oligosaccharyltransferase in HGG indicates its role in enhanced expression of glycoproteins. In-silico molecular docking with catalytic subunits of OST identified two small molecule inhibitors; Irinotecan and Entrectinib as potential candidates to target OST. We propose OST plays a major role in tumor metastasis by promoting EMT and could be used as a potential target to suppress glioma metastasis. Finally, the proteins identified in this study need further clinical research to validate their prognostic values as protein markers.