Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77401, USA.
Neuro Oncol. 2010 Jan;12(1):49-57. doi: 10.1093/neuonc/nop007. Epub 2009 Oct 20.
Only a subset of patients with newly diagnosed glioblastoma (GBM) exhibit a response to standard therapy. To date, a biomarker panel with predictive power to distinguish treatment sensitive from treatment refractory GBM tumors does not exist. An analysis was performed using GBM microarray data from 4 independent data sets. An examination of the genes consistently associated with patient outcome, revealed a consensus 38-gene survival set. Worse outcome was associated with increased expression of genes associated with mesenchymal differentiation and angiogenesis. Application to formalin fixed-paraffin embedded (FFPE) samples using real-time reverse-transcriptase polymerase chain reaction assays resulted in a 9-gene subset which appeared robust in these samples. This 9-gene set was then validated in an additional independent sample set. Multivariate analysis confirmed that the 9-gene set was an independent predictor of outcome after adjusting for clinical factors and methylation of the methyl-guanine methyltransferase promoter. The 9-gene profile was also positively associated with markers of glioma stem-like cells, including CD133 and nestin. In sum, a multigene predictor of outcome in glioblastoma was identified which appears applicable to routinely processed FFPE samples. The profile has potential clinical application both for optimization of therapy in GBM and for the identification of novel therapies targeting tumors refractory to standard therapy.
仅有一小部分新诊断的胶质母细胞瘤（GBM）患者对标准治疗有反应。迄今为止，尚无具有预测能力的生物标志物组合能够区分治疗敏感和治疗抵抗的 GBM 肿瘤。使用来自 4 个独立数据集的 GBM 微阵列数据进行了分析。对与患者预后一致相关的基因进行检查，揭示了一个共识的 38 个生存基因集。预后较差与间充质分化和血管生成相关基因的表达增加有关。使用实时逆转录聚合酶链反应（RT-PCR）检测在福尔马林固定石蜡包埋（FFPE）样本中的应用产生了一个在这些样本中似乎稳健的 9 个基因子集。然后在另一个独立的样本集中验证了这 9 个基因集。多变量分析证实，在调整临床因素和甲基鸟嘌呤甲基转移酶启动子甲基化后，9 个基因集是预后的独立预测因子。该基因集还与神经胶质瘤干细胞标志物（包括 CD133 和巢蛋白）呈正相关。总之，确定了胶质母细胞瘤预后的多基因预测因子，该因子似乎适用于常规处理的 FFPE 样本。该特征具有潜在的临床应用，既可以优化 GBM 的治疗，也可以确定针对标准治疗抵抗的肿瘤的新疗法。
