Department of Radiation Oncology, University of Arizona, Tucson, AZ 85719, USA.
College of Medicine, University of Arizona, Tucson Campus, Tucson, AZ 85724, USA.
Int J Mol Sci. 2024 Mar 25;25(7):3668. doi: 10.3390/ijms25073668.
The aim of this study was to investigate gene expression alterations associated with overall survival (OS) in glioblastoma (GBM). Using the Nanostring nCounter platform, we identified four genes (, and ) that achieved statistical significance when comparing GBM with non-neoplastic brain tissue. The four genes were included in a multivariate Cox Proportional Hazard model, along with age, extent of resection, and O6-methylguanine-DNA methyltransferase ( promotor methylation, to create a unique glioblastoma prognostic index (GPI). The GPI score inversely correlated with survival: patient with a high GPI had a median OS of 7.5 months (18-month OS = 9.7%) whereas patients with a low GPI had a median OS of 20.1 months (18-month OS = 54.5%; log rank -value = 0.004). The GPI score was then validated in 188 GBM patients from The Cancer Genome Atlas (TCGA) from a national data base; similarly, patients with a high GPI had a median OS of 10.5 months (18-month OS = 12.4%) versus 16.9 months (18-month OS = 41.5%) for low GPI (log rank -value = 0.0003). We conclude that this novel mRNA-based prognostic index could be useful in classifying GBM patients into risk groups and refine prognosis estimates to better inform treatment decisions or stratification into clinical trials.
本研究旨在探讨与胶质母细胞瘤(GBM)总生存期(OS)相关的基因表达变化。我们使用 Nanostring nCounter 平台,在比较 GBM 与非肿瘤性脑组织时,发现了四个具有统计学意义的基因(、和)。这四个基因被纳入了多变量 Cox 比例风险模型,同时还纳入了年龄、切除范围和 O6-甲基鸟嘌呤-DNA 甲基转移酶(MGMT)启动子甲基化,以创建一个独特的胶质母细胞瘤预后指数(GPI)。GPI 评分与生存呈负相关:GPI 评分高的患者中位 OS 为 7.5 个月(18 个月 OS = 9.7%),而 GPI 评分低的患者中位 OS 为 20.1 个月(18 个月 OS = 54.5%;对数秩检验值 = 0.004)。然后,我们在来自国家数据库的 188 名 GBM 患者中对 GPI 评分进行了验证;同样,GPI 评分高的患者中位 OS 为 10.5 个月(18 个月 OS = 12.4%),而 GPI 评分低的患者中位 OS 为 16.9 个月(18 个月 OS = 41.5%)(对数秩检验值 = 0.0003)。我们得出结论,这种新的基于 mRNA 的预后指数可用于将 GBM 患者分为风险组,并改善预后估计,以更好地为治疗决策或临床试验分层提供信息。