Abstract
Background and aimsGlioblastoma (GBM) is a common and aggressive primary brain tumor, and the prognosis for GBM patients remains poor. This study aimed to identify the key genes associated with the development of GBM and provide new diagnostic and therapies for GBM.MethodsThree microarray datasets (GSE111260, GSE103227, and GSE104267) were selected from Gene Expression Omnibus (GEO) database for integrated analysis. The differential expressed genes (DEGs) between GBM and normal tissues were identified. Then, prognosis-related DEGs were screened by survival analysis, followed by functional enrichment analysis. The protein–protein interaction (PPI) network was constructed to explore the hub genes associated with GBM. The mRNA and protein expression levels of hub genes were respectively validated in silico using The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) databases. Subsequently, the small molecule drugs of GBM were predicted by using Connectivity Map (CMAP) database.ResultsA total of 78 prognosis-related DEGs were identified, of which10 hub genes with higher degree were obtained by PPI analysis. The mRNA expression and protein expression levels of CETN2, MKI67, ARL13B, and SETDB1 were overexpressed in GBM tissues, while the expression levels of CALN1, ELAVL3, ADCY3, SYN2, SLC12A5, and SOD1 were down-regulated in GBM tissues. Additionally, these genes were significantly associated with the prognosis of GBM. We eventually predicted the 10 most vital small molecule drugs, which potentially imitate or reverse GBM carcinogenic status. Cycloserine and 11-deoxy-16,16-dimethylprostaglandin E2 might be considered as potential therapeutic drugs of GBM.ConclusionsOur study provided 10 key genes for diagnosis, prognosis, and therapy for GBM. These findings might contribute to a better comprehension of molecular mechanisms of GBM development, and provide new perspective for further GBM research. However, specific regulatory mechanism of these genes needed further elaboration.
Highlights
Background and aimsGlioblastoma (GBM) is a common and aggressive primary brain tumor, and the prognosis for GBM patients remains poor
protein–protein interaction (PPI) analysis revealed that centrin 2 (CETN2), marker of proliferation ki-67 (MKI67), ADP ribosylation factor like GTPase 13B (ARL13B), SET domain bifurcated histone lysine methyltransferase 1 (SETDB1), calneuron 1 (CALN1), ELAV like RNA binding protein 3 (ELAVL3), adenylate cyclase 3 (ADCY3), Synapsin II (SYN2), Solute car‐ rier family 12 member 5 (SLC12A5), and superoxide dismutase 1 (SOD1) with high degree of connectivity were selected as hub genes
For CETN2, MKI67, ARL13B, and SETDB1, patients with high expression experienced a worse OS, while high expression of CALN1, ELAVL3, ADCY3, SYN2, ARL13B, SLC12A5, and SOD1 were associated with better overall survival among patients with GBM
Summary
Glioblastoma (GBM) is a common and aggressive primary brain tumor, and the prognosis for GBM patients remains poor. This study aimed to identify the key genes associated with the development of GBM and provide new diagnostic and therapies for GBM. Glioblastoma (GBM) is a most common and aggressive malignant brain tumor, accounting for 16% of all primary brain and central nervous system neoplasms [1]. The mean survival of GBM is approximately 14.6 months, and GBM is one of the most challenging malignancies to treat due to its high heterogeneity, high recurrence rate, and diffusing invasiveness [2]. Despite extensive efforts to explore novel therapies, the survival of GBM has not markedly improved. It is necessary to develop effective treatment options. Gene therapy, molecularly targeted therapy, and immunotherapy are promising treatment approaches [3].
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