Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno 65653, Czech Republic, Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic, Central European Institute of Technology, Masaryk University, Brno 62500, Czech Republic.
Central European Institute of Technology, Masaryk University, Brno 62500, Czech Republic.
Carcinogenesis. 2014 Dec;35(12):2756-62. doi: 10.1093/carcin/bgu212. Epub 2014 Oct 16.
Glioblastoma multiforme (GBM) is the most malignant primary brain tumor. The prognosis of GBM patients varies considerably and the histopathological examination is not sufficient for individual risk estimation. MicroRNAs (miRNAs) are small, non-coding RNAs that function as post-transcriptional regulators of gene expression and were repeatedly proved to play important roles in pathogenesis of GBM. In our study, we performed global miRNA expression profiling of 58 glioblastoma tissue samples obtained during surgical resections and 10 non-tumor brain tissues. The subsequent analysis revealed 28 significantly deregulated miRNAs in GBM tissue, which were able to precisely classify all examined samples. Correlation with clinical data led to identification of six-miRNA signature significantly associated with progression free survival [hazard ratio (HR) 1.98, 95% confidence interval (CI) 1.33-2.94, P < 0.001] and overa+ll survival (HR 2.86, 95% CI 1.91-4.29, P < 0.001). O(6)-methylguanine-DNA methyltransferase methylation status was evaluated as reference method and Risk Score based on six-miRNA signature indicated significant superiority in prediction of clinical outcome in GBM patients. Multivariate Cox analysis indicated that the Risk Score based on six-miRNA signature is an independent prognostic classifier of GBM patients. We suggest that the Risk Score presents promising prognostic algorithm with potential for individualized treatment decisions in clinical management of GBM patients.
多形性胶质母细胞瘤（GBM）是最恶性的原发性脑肿瘤。GBM 患者的预后差异很大，组织病理学检查不足以进行个体风险评估。微小 RNA（miRNA）是一种小的非编码 RNA，作为基因表达的转录后调节剂发挥作用，并且反复证明在 GBM 的发病机制中发挥重要作用。在我们的研究中，我们对 58 例手术切除的 GBM 组织样本和 10 例非肿瘤脑组织进行了全 miRNA 表达谱分析。随后的分析显示，GBM 组织中有 28 个 miRNA 表达显著下调，能够精确地对所有检测样本进行分类。与临床数据的相关性导致确定了与无进展生存期显著相关的六 miRNA 特征[风险比（HR）1.98，95%置信区间（CI）1.33-2.94，P<0.001]和总生存期（HR 2.86，95%置信区间（CI）1.91-4.29，P<0.001）。O(6)-甲基鸟嘌呤-DNA 甲基转移酶甲基化状态被评估为参考方法，基于六 miRNA 特征的风险评分表明在预测 GBM 患者临床结局方面具有显著优势。多变量 Cox 分析表明，基于六 miRNA 特征的风险评分是 GBM 患者独立的预后分类器。我们建议风险评分提供了有前途的预后算法，具有在 GBM 患者的临床管理中进行个体化治疗决策的潜力。
