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