关键词: 多形性胶质母细胞瘤, 生物信息学, 基因表达综合数据库, 癌症基因组图谱数据库, 差异表达基因

Abstract:

Objective To analyze the key genes and candidate pathways related to the occurrence and development of glioblastoma multiforme （GBM） by bioinformatics methods， and to explore the pathogenesis and therapeutic targets of GBM. Methods Gene Expression Datasets TCGA-GBM and GSE7696 were obtained from The Cancer Genome Atlas （TCGA） Database and Gene Expression Omnibus （GEO） Database. Deseq2 and limma R Data Packages were used to screen the differentially expressed genes （DEGs） in GBM tissue and adjacent normal tissue， and the Gene Ontology （GO） fuctional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathway enrichment analysis were performed on the DEGs； the protein-protein interaction （PPI） network was analyzed by using the STRING Database； Cytoscape 3.9.1 Software was used to visualize the PPI network and perform the modular analysis. Results After the DEGs analysis of TCGA-GBM Transcription Data and Chip Dataset GSE7696， a total of 13 upregulated differentially expressed genes （UDEGs） and 77 downregulated differentially expressed genes （DDEGs） were obtained. The results of GO fuctional enrichment analysis showed that the DDEGs were mainly concentrated in the chloride channel activity， gamma-aminobutyric acid （GABA） receptor activity， GABA-gated chloride ion channel activity， GABA-A receptor activity， anterograde trans-synaptic signaling， chemical synaptic transmission and other biological processes. The KEGG signaling pathway were mainly concentrated in the GABA ergic synapse， neuroactive ligand-receptor interaction， neuro synapses containing serum， synaptic vesicle cycle and other signaling pathways. Two important gene modules were identified by PPI and module construction. The Cytoscape Software analysis results showed that solute carrier family 17 member 6（SLC17A6）， solute carrier family 1 member 2（SLC1A2），tachykinin precursor 1（TAC1），synaptotagmin 1（SYT1）， RNA binding fox-1 homolog 3（RBFOX3）， and gamma-aminobutyric acid type A receptor subunit gamma 2（GABRG2） were the key genes in PPI network. Conclusion SLC17A6，SLC1A2，TAC1，SYT1，RBFOX3，and GABRG2 genes may be involved in the occurrence and development of GBM，and the dysregulation of GABA ergic synaptic transmission related genes and pathway regulation network may be the main mechanism of pathogenesis of GBM.

Key words: Glioblastoma multiforme, Bioinformatics, Gene Expression Omnibus Database, The Cancer Genome Atlas Database, Differential expressed genes