Integrated Analysis to Evaluate the Prognostic Value of Signature mRNAs in Glioblastoma Multiforme

Abstract

Background: Gliomas are the most common intracranial tumors and are classified as I-IV. Among them, glioblastoma multiforme (GBM) is the most common invasive glioma with a poor prognosis. New molecular biomarkers that can predict clinical outcomes in GBM patients must be identified, which will help comprehend their pathogenesis and supply personalized treatment. Our research revealed four powerful survival indicators in GBM by reanalyzing microarray data and genetic sequencing data in public databases. Moreover, it unraveled new potential therapeutic targets which could help improve the survival time and quality of life of GBM patients. Materials and Methods: To identify prognostic signatures in GBMs, we analyzed the gene profiling data of GBM and standard brain samples from the Gene Expression Omnibus, including four datasets and RNA sequencing data from The Cancer Genome Atlas (TCGA) containing 152 glioblastoma tissues. We performed the differential analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, weighted gene co-expression network analysis (WGCNA) and Cox regression analysis. Results: After differential analysis in GSE12657, GSE15824, GSE42656 and GSE50161, overlapping differentially expressed genes were identified. We identified 110 up-regulated DEGs and 75 down-regulated DEGs in the GBM samples. Significantly enriched subclasses of the GO classification of these genes included mitotic sister chromatid separation, mitotic nuclear division and so on. In KEGG pathway analysis, the most abundant terms were ECM-receptor interaction and protein digestion and absorption. WGCNA analysis was performed on these 185 DEGs in 152 glioblastoma samples obtained from TCGA, and gene co-expression networks were constructed. We then performed a multivariate Cox analysis and established a Cox proportional hazards regression model using the top 20 genes significantly correlated with survival time. We

GNG5 is a novel oncogene associated with cell migration, proliferation, and poor prognosis in glioma

“…We found that high expression of GNG5 promotes the activation of a series of cancer-related signaling pathways (Figure 6). Similar interactions have been described previously; for example, the ECM-receptor interaction is involved in the proliferation and invasion of cancer cells [37,38], and focal adhesion is involved in the metastasis and invasion of cancer cells [39]. Additionally, the toll-like receptor promotes the immune evasion of glioma by down-regulating the MHC II molecules in microglia [40], and cell adhesion molecules and the nod-like receptor play a signi cant role in the proliferation, invasion, and metastasis of glioma cells [41][42][43][44].…”

GNG5 is a novel oncogene associated with poor prognosis in glioma patients

“…Similar interactions have been described previously; for example, the ECM-receptor interaction is involved in the proliferation and invasion of cancer cells [35,36], and focal adhesion is involved in the metastasis and invasion of cancer cells [37]. Additionally, the toll-like receptor promotes the immune evasion of glioma by down-regulating the MHC II molecules in microglia [38], and cell adhesion molecules and the nod-like receptor play a signi cant role in the proliferation, invasion, and metastasis of glioma cells [39][40][41][42].…”

GNG5 is a Novel Oncogene Associated with Poor Prognosis in Glioma Patients

“…6). Similar interactions have been described previously; for example, the ECM-receptor interaction is involved in the proliferation and invasion of cancer cells [35,36], and focal adhesion is involved in the metastasis and invasion of cancer cells [37]. Additionally, the toll-like receptor promotes the immune evasion of glioma by down-regulating the MHC II molecules in microglia [38], and cell adhesion molecules and the nod-like receptor play a signi cant role in the proliferation, invasion, and metastasis of glioma cells [39][40][41][42].…”