Glioblastoma Multiforme: Fewer Tumor Copy Number Segments of the SGK1 Gene Are Associated with Poorer Survival

摘要

Background/Aim: Glioblastoma multiforme (GBM) is the most common primary tumor of the central nervous system. The serum and glucocorticoid-regulated kinase SGK1 gene is required for the growth and survival of GBM stem-like cells under both normoxic and hypoxic conditions. It has been reported that oxygenation significantly affects cellular genetic expression; 30% of the genes required in hypoxia were not required under normoxic conditions. Therefore, we examined SGK1 expression to determine if it may be a novel potential drug target for GBM. Materials and Methods: We assessed the association between SGK1 and glioblastoma patient overall survival using the GBM cohort in TCGA (The Cancer Genome Atlas) database (TCGA-GBM). To access and analyze the data we used the UCSC Xena browser (https://xenabrowser.net). Survival data of the GBM subgroup were extracted for analysis and generation of Kaplan–Meier curves for overall survival. The best cut-off was identified by methods described in the R2 web-based application (http://r2.amc.nl). Results: We analyzed patient survival by tumor SGK1 copy number segments after removal of common germ-line copy-number variants (CNVs). Copy number segments (log2 tumorormal) ≤0.009700 were associated with significantly poorer survival (p=0.016). Conclusion: Increased median overall survival associated with increased SGK1 copy number segments may be a reflection of better tumor oxygenation. Therefore, besides being a drug target, SGK1 may also be a prognostic marker. Among molecular tumor markers, only the methylation status of the O-6-methylguanine-DNA methyltransferase (MGMT) gene has shown a significant association with survival in patients with GBM.