Research Institute of Modern Medicine, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China.
Eur J Cancer. 2010 Jun;46(9):1640-9. doi: 10.1016/j.ejca.2010.02.003. Epub 2010 Mar 8.
The aberrant expression of microRNAs (miRNAs) is associated with a variety of diseases including cancers. In the present study, the miRNA expression profile was examined in astrocytoma, a malignant and prevalent intracranial tumour in adults.
We screened the expression profile of 200 miRNAs in a training sample set consisting of 84 astrocytoma samples and 20 normal adjacent tissue (NAT) samples using the method of stem-loop quantitative RT-PCR. The significantly altered miRNAs were validated in another independent sample set consisting of 40 astrocytoma samples and 40 NAT samples. The correlation of the miRNA levels with survival in astrocytoma samples was estimated by performing Kaplan-Meier survival analysis and univariate/multivariate Cox proportional hazard regression analysis.
After a two-phase selection and validation process, seven miRNAs were found to have a significantly different expression profile in astrocytoma samples upon comparison to the NAT samples. Unsupervised clustering analysis further revealed the great potential of the 7-miRNA profile to differentiate between tumours and normal brain tissues. The down-regulation of hsa-miR-137 in astrocytomas was shown to be associated with advanced clinical stages of this disease. Using Kaplan-Meier survival analysis we showed that low expression of hsa-miR-181b or hsa-miR-106a, or high expression of hsa-miR-21 was significantly associated with poor patient survival. Moreover, Cox proportional hazard regression analysis revealed that this prognostic impact was independent of other clinicopathological factors.
Our results suggest a great potential for the use of miRNA profiling as a powerful diagnostic and prognostic marker in defining the signature of astrocytomas and in predicting the post-surgical outcome.
微小 RNA（miRNA）的异常表达与多种疾病有关，包括癌症。在本研究中，我们检查了星形细胞瘤中的 miRNA 表达谱，星形细胞瘤是成年人中一种恶性且常见的颅内肿瘤。
我们使用茎环定量 RT-PCR 方法筛选了由 84 例星形细胞瘤样本和 20 例正常邻近组织（NAT）样本组成的训练样本集中的 200 个 miRNA 的表达谱。在由 40 例星形细胞瘤样本和 40 例 NAT 样本组成的另一个独立样本集中验证了明显改变的 miRNA。通过进行 Kaplan-Meier 生存分析和单变量/多变量 Cox 比例风险回归分析来评估 miRNA 水平与星形细胞瘤样本中生存的相关性。
经过两阶段选择和验证过程，与 NAT 样本相比，在星形细胞瘤样本中发现有七种 miRNA 的表达谱具有显著差异。无监督聚类分析进一步显示，7-miRNA 谱在区分肿瘤和正常脑组织方面具有很大的潜力。星形细胞瘤中 hsa-miR-137 的下调被证明与这种疾病的晚期临床阶段有关。使用 Kaplan-Meier 生存分析，我们表明 hsa-miR-181b 或 hsa-miR-106a 的低表达或 hsa-miR-21 的高表达与患者生存不良显著相关。此外，Cox 比例风险回归分析表明，这种预后影响独立于其他临床病理因素。
我们的研究结果表明，miRNA 谱分析具有很大的潜力，可以作为一种强大的诊断和预后标志物，用于定义星形细胞瘤的特征，并预测手术后的结果。
