PO-510 Investigation of potential therapeutic targets by using in silico methods in glioblastoma

Abstract

IntroductionGlioblastoma is the one of the most common primary malignant tumour of brain. Due to anatomical and physiological characteristics of brain, drug delivery to the tumour site is hampered. In glioblastoma, survival time is short and recurrence is generally inevitable. The metastatic dissemination of glioblastoma is relatively rare but it could be more aggressive. Therefore, in vitro and in silico studies are accelerated in terms of the investigation of molecular characteristics of metastatic glioblastoma. The aim of this study, to investigate the expressed biomarkers of immigrant glioblastoma cells and potential therapeutic targets by using in silico methods.Material and methodsGEO (Gene Expression Omnibus) of the National Cancer Institute (NCI) provides is an international public repository of research society, which archives and freely distributes microarrays, next generation sequencing and other forms of high-resolution functional genomic data. Data set enumerated as GSE76018, is used for this research from GEO data portal. The data was analysed by using R software for statistical calculations and graphs. The level of the gene expression, and the resulting data were standardised by calculating a z-score, the fold changes (log2FC). As a threshold, | log2FC|≥2 and adjusted p-value was accepted as ≤0.05. Heat maps were drawn using a hierarchical clustering method in R-Bioconductor’s Heatplus library. Functional annotation tools and to understand biological meaning behind large list of genes analysed by using DAVID bioinformatics resources.Results and discussionsJAK-STAT pathway is found by using DAVID bioinformatics database. IFNA8, IL9, SOCS1, JAK3, CSH1, IFNL2 and IL12RB2 genes have played an active role in charge of protein coding Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3 pathway. So these genes affect the migration of glioblastomas and biomarkers is except to be effective at drug target. Sifalimumab and Rontalizumab connected to IFNA8, IL9 related to Enokizumab, also JAK3 linked to Tofacitinib.ConclusionAs a result of our investigation, JAK-STAT pathway, which is known to be an important mediator of tumour cell survival, growth and invasion in glioblastomas was, identified the migratory phenotype indicator. In this pathway, seven genes as therapeutic targets and related drugs potentially identified. Further in vitro and in vivo validation studies should be done for the confirmation for the provided biomarkers and therapeutic targets.