Identification of Key Genes and Pathwaysin Glioblastoma Patients, with Histon۳.۳ (H۳F۳A) mutationsby Integrated Bioinformatics Analysis

Background: Glioblastoma is a kind of brain tumor whichcharacterized by high mortality, prevalence and poor prognosis.So choosing the most effective strategies such as diagnosisof molecular mechanisms and interactions, seems necessaryto treatment of malignant glioma. For this aim, bioinformaticsanalysis of microarray data was applied to find the associationof decreased and increased genes and relevant miRNAs in glioblastomapatient.Materials and Methods: The microarray datasets GSE۳۴۸۲۴,GSE۳۶۲۴۵ and GSE۴۹۸۲۲ which was composed of gene expressiondata by using the [HG-U۱۳۳_Plus_۲] Affymetrix HumanGenome U۱۳۳ Plus ۲.۰ Array(GPL۵۷۰) platform, were downloadedfrom the GEO database. Each dataset was processed byusing the log۲ transformation and normalized by Package ofAffy and RMA in R software. Adjusted P.value of <۰.۰۵ was setas the cut-off criteria for differently expressed genes (DEGs).DEGs with P.value <۰.۰۵ and fold change (|FC|)>۲ were selectedas biomarkers in all three datasets. Functional and pathwayenrichment analysis were performed by using the BioDB andEnrichR databases, although, protein– protein interaction (PPI)network was constructed by Cytoscape software.Results: ۵۶۹ Gene in three datasets showed significantly differencesexpression levels (P.value <۰.۰۵), among them, approximately۴۲۹ genes showed Up regulation and ۱۴۰ genesdown regulation with log Fold change more than ۲. To assessthe function of the DEGs, the gene ontology (GO), Kyoto Encyclopediaof Genes and Genomes (KEGG) and pathway enrichmentanalyses from EnrichR were used. It is showed that up regulated genes were enriched in voltage-gated sodium channelactivity, ion channel activity, in organic molecular entity andtransmembrane transporter activity and down regulated genesenriched in RNA polymerase II regulatory region, sequencespecificDNA binding and DNA- binding transcription factoractivity.Conclusion: By more closely examining these genes and theirfunction in the cell, we can find new solutions for early diagnosisand targeted treatment of this cancer.

Keywords:

GBM , Glioblastoma , Microarray analysis , GEO۲R