Screening the Significant Hub Genes by Comparing Tumor Cells, Normoxic and Hypoxic Glioblastoma Stem-like Cell Lines Using Co-Expression Analysis in Glioblastoma

Abstract

Glioblastoma multiforme (GBM) is categorized by rapid malignant cellular growth in the central nervous system (CNS) tumors. It is one of the most prevailing primary brain tumors, particularly in human male adults. Even though the combination therapy comprises surgery, chemotherapy, and adjuvant therapies, the survival rate is on average 14.6 months. Glioma stem cells (GSCs) have key roles in tumorigenesis, progression, and counteracting chemotherapy and radiotherapy. In our study, firstly, the gene expression dataset GSE45117 was retrieved and differentially expressed genes (DEGs) were spotted. The co-expression network analysis was employed on DEGs to find the significant modules. The most significant module resulting from co-expression analysis was the turquoise module. The turquoise module related to the tumor cells, hypoxia, normoxic treatments of glioblastoma tumor (GBT), and GSCs were screened. Sixty-one common genes in the turquoise module were selected generated through the co-expression analysis and protein–protein interaction (PPI) network. Moreover, the GO and KEGG pathway enrichment results were studied. Twenty common hub genes were screened by the NetworkAnalyst web instrument constructed on the PPI network through the STRING database. After survival analysis via the Kaplan–Meier (KM) plotter from The Cancer Genome Atlas (TCGA) database, we identified the five most significant hub genes strongly related to the progression of GBM. We further observed these five most significant hub genes also up-regulated in another GBM gene expression dataset. The protein–protein interaction (PPI) network of the turquoise module genes was constructed and a KEGG pathway enrichments study of the turquoise module genes was performed. The VEGF signaling pathway was emphasized because of the strong link with GBM. A gene–disease association network was further constructed to demonstrate the information of the progression of GBM and other related brain neoplasms. All hub genes assessed through this study would be potential markers for the prognosis and diagnosis of GBM.

MRI Elastography Identifies Regions of Extracellular Matrix Reorganization Associated with Shorter Survival in Glioblastoma Patients

“…Several of the genes found in our study to be upregulated in 'stiff' biopsies have previously been shown to play a role in glioma malignancy. NRP1 and DAB2 have been linked to glioma progression 35,36 , PECAM1 correlates with GBM aggressiveness 37 , CD163 is positively associated with the glioma malignancy grade 38 , and Flt1 promotes invasion and migration of glioblastoma cells 39 . CR1, PLAGL1, COL4A1, and COL5A2 have all been shown to correlate with shorter survival [40][41][42][43] .…”

Potential diagnostic and drug target markers in glioblastoma

“…Additionally, the functions of the target genes in GBM were retrieved from several databases, including PubMed, CTD, and OMIM 31 . Cytoscape software version 3.6 was used to illustrate the network to investigate the significance of source (DEGs) and target proteins in patients with glioblastoma 32 , 33 .…”

Canine glioma stem-like cells demonstrate DNA methylation-dependent enhancement of cellular respiration following low oxygen tension

“…To evaluate similarities between canine and human GSC biology under hypoxic stress, we compared genes that were differentially methylated in our canine lines to genes that were differentially expressed in human adult (GBM) and pediatric (DIPG) glioma. Utilizing publicly available microarray datasets 11,34 , Gene Set Enrichment Analysis (GSEA) demonstrated a positive correlation between genes that were signi cantly hypomethylated in canine GSLCs and orthologous genes with increased mRNA expression in GBM GSCs (Figure 6A; normalized enrichment score (NES) = 1.87, p<0.01). There was no correlation between signi cantly hypermethylated canine genes and orthologous genes in human GBM GSCs (Figure 6B; NES: 1.04, p=0.35).…”