Department of Neurosurgery and Neuropathology, Kyushu University, Fukuoka, Japan.
Clin Cancer Res. 2010 Aug 15;16(16):4289-97. doi: 10.1158/1078-0432.CCR-10-0207. Epub 2010 Jul 2.
MicroRNAs (miRNA) are short noncoding RNAs that can play critical roles in diverse biological processes. They are implicated in tumorigenesis and function both as tumor suppressors and as oncogenes. The clinical significance of miRNA expression profiles in malignant gliomas remains unclear.
In this study, we examined the expression levels of 365 mature human miRNAs in 12 malignant gliomas, including 8 glioblastomas and 4 anaplastic astrocytomas, using TaqMan real-time quantitative PCR arrays. A validation study was done to corroborate a subset of the results, including expression levels of miR-196a, -196b, -21, and -15b, by analyzing 92 malignant gliomas by conventional real-time PCR. We modeled the relationship between the expression levels of these miRNAs and the survival rate of 39 glioblastoma patients by Kaplan-Meier method and multivariate analysis.
Expression profiles in glioblastomas and anaplastic astrocytomas suggested that 16 miRNAs were candidate markers associated with the malignant progression of gliomas. Among them, miR-196a showed the most significant difference (P = 0.0038), with miR-196b also having a high significance (P = 0.0371). Both miRNAs showed increased expression levels in glioblastomas relative to both anaplastic astrocytomas and normal brains in the validation study. Furthermore, patients with high miR-196 expression levels showed significantly poorer survival by the Kaplan-Meier method (P = 0.0073). Multivariate analysis showed that miR-196 expression levels were an independent predictor of overall survival in all 39 glioblastoma patients (P = 0.021; hazard ratio, 2.81).
Our results suggest that miR-196 may play a role in the malignant progression of gliomas and may be a prognostic predictor in glioblastomas.
微小 RNA（miRNA）是一类短的非编码 RNA，可以在多种生物学过程中发挥关键作用。它们被认为与肿瘤发生有关，并作为肿瘤抑制因子和癌基因发挥作用。miRNA 表达谱在恶性神经胶质瘤中的临床意义尚不清楚。
在这项研究中，我们使用 TaqMan 实时定量 PCR 阵列检测了 12 例恶性神经胶质瘤（包括 8 例胶质母细胞瘤和 4 例间变性星形细胞瘤）中 365 种成熟人类 miRNA 的表达水平。通过常规实时 PCR 分析 92 例恶性神经胶质瘤，验证了一部分结果，包括 miR-196a、-196b、-21 和 -15b 的表达水平。我们通过 Kaplan-Meier 方法和多变量分析来模拟这些 miRNA 的表达水平与 39 例胶质母细胞瘤患者生存率之间的关系。
胶质母细胞瘤和间变性星形细胞瘤的表达谱表明，有 16 种 miRNA 是与胶质瘤恶性进展相关的候选标志物。其中，miR-196a 的差异最显著（P=0.0038），miR-196b 也具有较高的显著性（P=0.0371）。在验证研究中，这两种 miRNA 在胶质母细胞瘤中的表达水平均高于间变性星形细胞瘤和正常脑组织。此外，Kaplan-Meier 法显示 miR-196 高表达的患者生存率显著降低（P=0.0073）。多变量分析显示，miR-196 表达水平是所有 39 例胶质母细胞瘤患者总生存的独立预测因子（P=0.021；危险比，2.81）。
我们的研究结果表明，miR-196 可能在神经胶质瘤的恶性进展中发挥作用，并可能是胶质母细胞瘤的预后预测因子。
