Developing Novel Targeted Theraphies Towards High Grade Glioma by Using Omics Data Integration Approaches

Gliomas are the brain tumors that develop in glial cells and present severechallenges based on intertumoral heterogeneity associated with different subtypes,further leading to poor prognosis and outcomes for patients. This study was conductedto utilize the transcriptomics and DNA methylation datasets available to researchersto arrive at conclusions that can be utilized for either screening novel targets or usealready established drugs that can target the specific gene signatures associated withlow grade gliomas (LGGs), which develop into high grade gliomas (HGGs) orGlioblastoma multiforme (GBM). We identified co-expression modules and theirassociated pathways for specific subtypes of LGG IDH mut pTERT-, IDH mutpTERT+, IDH wt pTERT-, and IDH wt pTERT+. We constructed co-expressionmodules based on these subtypes and found common and different enriched pathwaysas synapse pathways and immune-related pathways, respectively. We further exploredthe differentially expressed genes (DEGs) and found a gene signature of upregulatedGNG12 and downregulated PLCB1, GRIA2, GABRA3, and GNAL after mappingDEGs on our co-expression modules of interest. This gene signature was included inour drug-gene interaction analysis, leading us to 4 drugs (Vemurafenib, VanadiumPentoxide, Imatinib, and Cisplatin,) that can target 4 out of 5 genes. Therefore, werecommend exploring the synergistic effects of the combination of these drugs againstlow and high grade gliomas. We also integrated transcriptomics and DNA methylationdata to develop networks including epigenetic factors that can be targeted in a subtypespecific manner. Our analysis revealed that PRMT5 can be used as a target irrespectiveof the LGG subtype and WEE1 is a specific target for IDH wt regardless of pTERTstatus. The specific chemical inhibitors of these targets being available could facilitatetranslation of our findings into preclinical settings.