miR-182 作为胶质瘤进展和患者生存的预后标志物。
miR-182 as a prognostic marker for glioma progression and patient survival.
机构信息
Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou, Guangdong 510080, China.
出版信息
Am J Pathol. 2010 Jul;177(1):29-38. doi: 10.2353/ajpath.2010.090812. Epub 2010 May 14.
Accumulating evidence indicates that miRNA expression can be used as a diagnostic and prognostic marker for human cancers. We report that the expression level of miR-182 was markedly up-regulated in glioma cell lines and in human primary glioma specimens. Quantitative PCR analysis showed that miR-182 was significantly increased by up to 32-fold in glioma tumors compared with the adjacent nontumor brain tissues obtained from the same patient. Elevated expression of miR-182 was further identified by in situ hybridization in 248 of 253 (98%) archived human glioma biopsies tested. Statistical analysis revealed a significant correlation between miR-182 expression and World Health Organization glioma grading (P < 0.001). The cumulative 5-year survival rate of glioma patients was 51.54% (95% confidence interval, 0.435 to 0.596) in the low miR-182-expression group, whereas it was only 7.23% (95% confidence interval, 0.027 to 0.118) in the high miR-182-expression group (P = 0.001), and multivariate Cox regression analysis indicated that miR-182 expression was an independent prognostic indicator for the survival of glioma patients. Moreover, the correlations of miR-182 level with the clinical features of glioma suggested in the in situ hybridization analysis were further verified by the real-time RT-PCR analysis. Taken together, our results suggest that miR-182 could be a valuable marker of glioma progression and that high miR-182 expression is associated with poor overall survival in patients with malignant glioma.
越来越多的证据表明,miRNA 的表达可以作为人类癌症的诊断和预后标志物。我们报告说,miR-182 的表达水平在神经胶质瘤细胞系和人原发性神经胶质瘤标本中明显上调。定量 PCR 分析显示,与同一患者获得的相邻非肿瘤脑组织相比,胶质瘤肿瘤中 miR-182 的表达增加了高达 32 倍。在 253 例存档的人类神经胶质瘤活检中,通过原位杂交进一步鉴定出 miR-182 的高表达(248/253,98%)。统计分析显示,miR-182 表达与世界卫生组织神经胶质瘤分级之间存在显著相关性(P<0.001)。在低 miR-182 表达组中,神经胶质瘤患者的 5 年累积生存率为 51.54%(95%置信区间,0.435 至 0.596),而在高 miR-182 表达组中,生存率仅为 7.23%(95%置信区间,0.027 至 0.118)(P=0.001),多变量 Cox 回归分析表明 miR-182 表达是神经胶质瘤患者生存的独立预后指标。此外,通过实时 RT-PCR 分析进一步验证了原位杂交分析中 miR-182 水平与神经胶质瘤临床特征的相关性。总之,我们的研究结果表明,miR-182 可能是神经胶质瘤进展的一个有价值的标志物,高 miR-182 表达与恶性神经胶质瘤患者的总体生存率降低相关。