Li Fubin, Li Yiping, Zhang Kewei, Li Ye, He Ping, Liu Yujia, Yuan Hongyan, Lu Honghua, Liu Jinxiang, Che Songtian, Li Zhenju, Bie Li
Department of Neurosurgery of the First Clinical Hospital.
Department of Immunology, Norman Bethune College of Medicine.
Onco Targets Ther. 2017 Jan 16;10:387-395. doi: 10.2147/OTT.S117165. eCollection 2017.
Glioblastoma multiforme (GBM) is the most common malignant and lethal type of primary central nervous system tumor in humans. In spite of its high lethality, a small percentage of patients have a relatively good prognosis, with median survival times of 36 months or longer. The identification of clinical subsets of GBM associated with distinct molecular genetic profiles has made it possible to design therapies tailored to treat individual patients.
We compared microarray data sets from long-term survivors (LTSs) and short-term survivors (STSs) to screen for prognostic biomarkers in GBM patients using the WebArrayDB platform. We focused on , , and , all members of a group of 10 of the most promising, differentially regulated gene candidates. Using formalin-fixed paraffin-embedded GBM samples, we corroborated the relationship between these genes and patient outcomes using methylation-specific polymerase chain reaction (PCR) for methylation status and quantitative reverse transcription PCR for expression of these genes.
Expression levels of the mRNAs of these 3 genes were higher in the GBM samples than in normal brain samples and these 3 genes were significantly upregulated in STSs compared to the levels in LTS samples (<0.01). Furthermore, Kaplan-Meier analysis showed that the expression patterns of and serve as independent prognostic indicators for overall survival (<0.01 and <0.05, respectively).
To our knowledge, this is the first report describing as a prognostic factor for GBM patient survival, demonstrating that increased GBM survival time correlates with decreased expression. Understanding expression patterns could aid in the creation of powerful tools to predict clinical prognoses of GBM patients.
多形性胶质母细胞瘤（GBM）是人类原发性中枢神经系统肿瘤中最常见的恶性致死性肿瘤类型。尽管其致死率很高，但仍有一小部分患者预后相对较好，中位生存时间为36个月或更长。对与不同分子遗传特征相关的GBM临床亚组的识别使得设计针对个体患者的治疗方法成为可能。
我们使用WebArrayDB平台比较了长期存活者（LTSs）和短期存活者（STSs）的微阵列数据集，以筛选GBM患者的预后生物标志物。我们重点关注了 、 和 ，它们是一组10个最有前景、差异调节的基因候选物中的成员。使用福尔马林固定石蜡包埋的GBM样本，我们通过甲基化特异性聚合酶链反应（PCR）检测 甲基化状态以及通过定量逆转录PCR检测这些基因的表达，证实了这些基因与患者预后之间的关系。
这3个基因的mRNA在GBM样本中的表达水平高于正常脑样本，并且与LTS样本中的水平相比，这3个基因在STSs中显著上调（<0.01）。此外，Kaplan-Meier分析表明， 和 的表达模式分别作为总生存期的独立预后指标（分别为<0.01和<0.05）。
据我们所知，这是第一份将 描述为GBM患者生存预后因素的报告，表明GBM生存时间延长与 表达降低相关。了解 表达模式有助于创建强大的工具来预测GBM患者的临床预后。
