Omics veri entegrasyon yaklaşımlarını kullanarak yüksek dereceli gliomaya (HGG) yönelik yeni hedefli tedavilerin geliştirilmesi

Gliomas are the brain tumors that develop in glial cells and present severe challenges based on intertumoral heterogeneity associated with different subtypes, further leading to poor prognosis and outcomes for patients. This study was conducted to utilize the transcriptomics and DNA methylation datasets available to researchers to arrive at conclusions that can be utilized for either screening novel targets or use already established drugs that can target the specific gene signatures associated with low grade gliomas (LGGs), which develop into high grade gliomas (HGGs) or Glioblastoma multiforme (GBM). We identified co-expression modules and their associated pathways for specific subtypes of LGG IDH mut pTERT-, IDH mut pTERT+, IDH wt pTERT-, and IDH wt pTERT+. We constructed co-expression modules based on these subtypes and found common and different enriched pathways as synapse pathways and immune-related pathways, respectively. We further explored the differentially expressed genes (DEGs) and found a gene signature of upregulated GNG12 and downregulated PLCB1, GRIA2, GABRA3, and GNAL after mapping DEGs on our co-expression modules of interest. This gene signature was included in our drug-gene interaction analysis, leading us to 4 drugs (Vemurafenib, Vanadium Pentoxide, Imatinib, and Cisplatin,) that can target 4 out of 5 genes. Therefore, we recommend exploring the synergistic effects of the combination of these drugs against low and high grade gliomas. We also integrated transcriptomics and DNA methylation data to develop networks including epigenetic factors that can be targeted in a subtype specific manner. Our analysis revealed that PRMT5 can be used as a target irrespective of the LGG subtype and WEE1 is a specific target for IDH wt regardless of pTERT status. The specific chemical inhibitors of these targets being available could facilitate translation of our findings into preclinical settings. Keywords: Glioblastoma, Lower Grade Glioma, Transcriptomics, Co-expression Analysis, DNA Methylation, Bioinformatics Pipeline, Drug-Gene Interaction