Development of a gene expression–based prognostic signature for IDH wild-type glioblastoma

摘要: BACKGROUND We aimed to develop a gene expression-based prognostic signature for isocitrate dehydrogenase (IDH) wild-type glioblastoma using clinical trial datasets representative of populations. METHODS Samples were collected from newly diagnosed patients with IDH in the ARTE, TAMIGA, EORTC 26101 (referred as "ATE"), AVAglio, and GLARIUS trials, or treated at UCLA. Transcriptional profiling was achieved NanoString expression platform. To identify genes overall survival (OS), we built an elastic net penalized Cox proportional hazards regression model discovery ATE dataset. For validation independent (AVAglio, GLARIUS, UCLA), combined net-selected into robust z-score (ATE score) overcome platform differences between cohorts. RESULTS data available 512 Elastic identified 9 (CHEK1, GPR17, IGF2BP3, MGMT, MTHFD1L, PTRH2, SOX11, S100A9, TFRC). Translating weighted scores score conserved value genes. The OS dataset (P < 0.0001), expected, cohorts P < 0.0001; P = 0.02; UCLA, P = 0.004). remained following adjustment O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status corticosteroid use baseline. A positive correlation proneural/proliferative subtypes observed MGMT non-methylated status. CONCLUSIONS showed may enable stratification glioblastoma.