Glioblastoma multiforme (GBM) is a highly lethal, stage IV brain tumor with a prevalence of approximately 2 per 10000 people globally. The cell surface proteins or surfaceome play significant roles in modulating cancer phenotypes and acting as information gateway in many oncogenic signaling pathways. Hence, surfaceome are attractive targets for cancer therapy due to their direct accessibility to drugs. Nonetheless, a comprehensive GBM surfaceome landscape has not been fully defined. Thus, the aim of this study is to define GBM-specific surfaceome genes and identify key cell surface genes that could potentially be developed as novel GBM biomarkers, or therapeutically targeted.
We integrated the RNA-Seq data from TCGA GBM (n=166) and GTEx normal brain cortex (n=408) databases to identify the significantly dysregulated surfaceome in GBM. This was followed by integrative analysis that combines transcriptomics, proteomics and protein-protein interaction network data to prioritize the high-confidence GBM surfaceome signature.
Among the 2,381 significantly dysregulated genes in GBM, 395 genes were classified as surfaceome. Via the integrative analysis, we identified 6 high-confidence GBM molecular signature, HLA-DRA, CD44, SLC1A5, EGFR, ITGB2, PTPRJ, which were significantly upregulated in GBM. The expression of these genes were validated in an independent transcriptomics database, which confirmed their upregulated expression in GBM. Importantly, high expression of CD44, PTPRJ and HLA-DRA is significantly associated with poor disease-free survival. Lastly, using the Drugbank database, we identified several clinically-approved drugs targeting the GBM molecular signature suggesting potential drug repurposing.
In summary, we identified and highlighted the key GBM surface-enriched repertoires that could be biologically relevant in supporting GBM pathogenesis. These genes could be further interrogated experimentally in future studies that could lead to efficient GBM diagnostic/prognostic markers or a therapeutic regimen to treat GBM.