脑胶质瘤中miR-181b的表达及临床意义

背景与目的：miR-181b在多种肿瘤中表达异常，并参与调节多种抗肿瘤药物的敏感性。研究发现miR-181b在胶质瘤中具有起类似抑癌基因的作用．可作为胶质瘤的独立预后指标。本研究旨在进一步探讨恶性胶质瘤中miR-181b表达的临床意义及miR-181b对替莫唑胺化疗敏感性的影响。方法：收集不同病理级别胶质瘤标本，以荧光定量PCR法检测其中miR-181b的表达，分析其与胶质瘤病理分级及患者预后的关系：利用CCK-8细胞毒性实验检测患者恶性胶质瘤细胞对替莫唑胺的敏感性。并分析其与miR-181b表达的关系。结果：miR-181b在胶质瘤组织中的表达显著低于正常脑组织伊〈0．051．miR-181b的表达水平分别为：正常脑组织3．69±0．477，WH0I级2．56±0．354．WHOⅡ级0．81±0．222．WHOⅢ级0．42±0．130．WH0 Ⅳ级0．21±0．067。miR-181b表达低的患者中位生存期为370±37天．而miR-181b表达高的患者中位生存期为493±60天（P〈0．05）。在高级别胶质瘤中，miR-181b的表达与替莫唑胺的敏感性呈正相关（r=-0．576，P〈0．001）。结论：miR-181b在胶质瘤中的表达与胶质瘤的病理级别呈负相关．而与脑胶质瘤患者预后呈正相关．与高级别胶质瘤对替莫唑胺的敏感性呈正相关．

miR-181b Expression in Human Gliomas and Its Clinical Significance

BACKGROUND ＆ OBJECTIVE： It has been reported that miR-181b was downregulated in several cancer types and the aberrant expression was associated with drug resistance, miR-181h is known to function as a turnout suppressor gene and serves as a prognostic marker in human glioma. The purpose of this study is to evaluate miR-181b expression in gliomas and its clinical significance, as well as to temozolomide（TMZ） sensitivity. METHODS： The expression level of miR-181b was measured by qRT-PCR for frozen h to determine growth inhibiting effects of temozolomide uman glioma specimens. CCK-8 was used （TMZ） on the primary glioma samples. RESULTS： miR-181b expression in normal brain tissu±e and glioma samples of WHO grade I, II, IIIand IV was 3.69 ± 0.477, 2.56 ± 0.354, 0.81 ± 0.222, 0.42 ± 0.130 and 0.21 ± 0.067, respectively. There were significant differences between normal brain and each glioma groups （P 〈 0.05）. Median survival time of patientswith low level of miR-181b was 370 ± 37 days, while with high level of miR-181b was 493 ± 60 days. TMZ Sensitivity was measured for 48 high grade gliomas （WHO m/IV） , it showed significant positive association with miR-181b expression （r=-0.576, P 〈 0.001）. CONCLUSIONS： miR-181b expression is generally lower in human gliomas, and is negatively associated to tumor grade but positively to prognosis of the patients. The miR-181b expression level is also positively correlated to temozolomide sensitivity in high grade gliomas.