Yan Wei, Li Rui, Liu Yanwei, Yang Pei, Wang Zheng, Zhang Chuanbao, Bao Zhaoshi, Zhang Wei, You Yongping, Jiang Tao
Beijing Neurosurgical Institute, Capital Medical University, Beijing, PR China. Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
Oncotarget. 2014 Dec 30;5(24):12908-15. doi: 10.18632/oncotarget.2679.
MicroRNAs (miRNAs) are directly involved in the progression in various cancers. To date, no systematic researches have been performed on the expression pattern of miRNA during progression from low grade gliomas to anaplastic gliomas or secondary glioblastomas and those prognostic miRNAs in anaplastic gliomas and secondary glioblastomas. In the present study, high-throughput microarrays were used to measure miRNA expression levels in 116 samples in the different progression stages of glioma. We found that miRNA expression pattern totally altered when low grade gliomas progressed to anaplastic gliomas or secondary glioblastomas. However, anaplastic gliomas and secondary glioblastomas have similar expression pattern in miRNA level. Furthermore, we developed a five-miRNA signature (two protective miRNAs-miR-767-5p, miR-105; three risky miRNAs: miR-584, miR-296-5p and miR-196a) that could identify patients with a high risk of unfavorable outcome in anaplastic gliomas regardless of histology type. It should be highlighted that the five-miRNA signature can also identify patients who had a high risk of unfavorable outcome in secondary and TCGA Proneural glioblastomas, but not Neural, Classical and Mesenchymal glioblastomas. Taken together, our results demonstrate that miRNA expression patterns in the malignant progression of gliomas and a novel prognostic classifier, the five-miRNA signature, serve as a prognostic marker for patient risk stratification in anaplastic gliomas, Secondary and Proneural glioblastomas.
微小RNA(miRNA)直接参与多种癌症的进展。迄今为止,尚未对miRNA在低级别胶质瘤进展为间变性胶质瘤或继发性胶质母细胞瘤过程中的表达模式以及间变性胶质瘤和继发性胶质母细胞瘤中的预后相关miRNA进行系统研究。在本研究中,使用高通量微阵列来测量116个不同胶质瘤进展阶段样本中的miRNA表达水平。我们发现,当低级别胶质瘤进展为间变性胶质瘤或继发性胶质母细胞瘤时,miRNA表达模式完全改变。然而,间变性胶质瘤和继发性胶质母细胞瘤在miRNA水平上具有相似的表达模式。此外,我们开发了一种五miRNA特征(两个保护性miRNA——miR-767-5p、miR-105;三个风险miRNA:miR-584、miR-296-5p和miR-196a),该特征可以识别间变性胶质瘤中预后不良风险高的患者,而不考虑组织学类型。需要强调的是,该五miRNA特征也可以识别继发性和TCGA易发性神经胶质母细胞瘤中预后不良风险高的患者,但不能识别神经型、经典型和间充质型胶质母细胞瘤。综上所述,我们的结果表明,胶质瘤恶性进展过程中的miRNA表达模式以及一种新的预后分类器——五miRNA特征,可作为间变性胶质瘤、继发性和易发性神经胶质母细胞瘤患者风险分层的预后标志物。