Computational analysis and verification of molecular genetic targets for glioblastoma

Abstract

Background: Glioblastoma (GBM) is the most common malignant brain tumor with a poor prognosis. The initial treatment for high-grade gliomas is surgical excision. However, even with concomitant use of radiation or chemotherapy, patients are still prone to recurrence. The specific pathogenesis of GBM is still controversial. Methods: Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) between GBM and normal brain tissues were screened. P-value was obtained by Bayes test based on the limma package. Statistical significance was set as P-value <0.05 and |Fold change (FC)| > 0.2 (GSE90886); P-value <0.05 and |FC| > 1 (GSE116520, GSE103228). Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG), protein–protein interaction (PPI) network were performed. Hub genes were selected from miRNA target genes and DEGs. GBM and normal brain tissues were extracted to verify the expression. Results: A total of 100 DEGs were overlapped in both datasets. Analysis of pathways and process enrichment tests indicated that ion transport, positive regulation of macromolecule metabolic process, cell cycle, axon guidance were enriched in the GBM. Sixteen hub genes were identified. Hub genes ADARB1 and neuropilin 1 (NRP1) were significantly associated with overall survival (OS) and disease-free survival (DFS) (P<0.05). Eukaryotic translation termination factor 1 (ETF1) was associated with DFS (P<0.05). Conclusions: DEGs and DEMs were found between GBM tumor tissues and normal brain tissues. These biomarkers may be used as targets for early diagnosis and specific treatment.

Genomic profiling of cancerous patients identifies FPR2 as an alternative immunotherapeutic target in glioblastoma multiforme

“…The RT-qPCR analysis was done to detect the expressions of 6 hub genes (FPR2, VEGFA, SERPINA1, SOX2, PBK, ITGB3) ( Supplementary 1 ) to validate the results in the bioinformatics analysis. The expression of all of the 6 genes was significantly increased in glioma cell lines compared to a different extent compared to the HEB cell line ( Figure 4 ), which further verify the differential analysis results [41]. Among these investigated hub genes, FPR2 has the highest expression levels.…”

“…These genes played a significant role in the biological pathway leading to GBM progression, as a result, our ensuing research was focused on investigating the interrelationship between these key genes and tumor activity in GBM patients. (Figure 4), which further verify the differential analysis results [41]. Among these investigated hub genes, FPR2 has the highest expression levels.…”

“…In this study, we aimed to identify the differentially expressed genes in glioblastoma multiforme and normal control tissue, which could be used as potential targets for glioma therapy or prediction for the cancer progression [41, 45]. We identified 7,147 up-regulated genes and 6,528 differently expressed genes that were shared between GBM and Control Group.…”

“…The current average survival rate of GBM patients is within 15 months of diagnosis [3], and less than 5% have a 5-year survival rate [40]. Difficulty in achieving full removal of tumors as tumor cells has been encountered since GBM disseminates within the brain, which also significantly diminishes the efficacy of surgery and radiotherapy [37, 41], even though sub-total resection has associated with increasing survival [5]. TTF combination therapy also incurs a prohibitive monthly treatment cost of $20,000 for many GBM patients [4].…”

Prognostic value of immune-related genes in laryngeal squamous cell carcinoma

“…Eukaryotic translation termination factor 1 ( ETF1 ) is mainly involved in the regulation of translation release factor activity, protein methylation and autophagy ( 47 ). Abnormal expression of ETF1 can participate in the progression of many cancers, including breast cancer and glioblastoma ( 48 ). Moreover, ETF1 could produce potential oncogenic abnormal proteins and be a potential therapeutic target for myeloid tumors ( 49 ).…”