CAJ | 학술논문

目的探讨NF2、TIMP-3和THBS1基因甲基化在脑膜瘤发生、发展中的作用及其在脑膜瘤的早期诊断、治疗和预后评估中的价值.方法收集山东大学齐鲁医院1992至2005年手术治疗的66例脑膜瘤患者的标本,其中单发性脑膜瘤30例,多发性脑膜瘤36例,对所有标本进行诊断、组织学分型和分级,提取基因组DNA,以正常脑组织做对照,用甲基化特异的PCR (MSP)法,检测肿瘤组织标本中基因甲基化的情况,统计分析单发性脑膜瘤、多发性脑膜瘤及不同级别脑膜瘤之间甲基化率差异.结果 30例单发性脑膜瘤中NF2、TIMP-3和THBS1基因甲基化率分别是26.7％(8/30)、16.7％(5/30)和36.7％(11/30)；36例多发性脑膜瘤中3种基因的甲基化率分别是30.6％(11/36)、22.2％(8/36)和22.2％(8/36),而正常脑组织中3种基因均未检测到甲基化现象.Ⅰ～Ⅲ级脑膜瘤中单发和多发性者3种基因的甲基化率差异均无统计学意义.而单发性、多发性脑膜瘤Ⅰ和Ⅱ、Ⅲ级间3种基因差异有统计学意义,而Ⅱ、Ⅲ级间差异无统计学意义.结论 NF2、TIMP-3和THBS1基因甲基化与非典型性和间变性脑膜瘤的发生、发展有关,也是脑膜瘤癌变的重要原因,有助于脑膜瘤的临床诊断,为脑膜瘤的早期发现提供帮助.
목적 탐토NF2、TIMP-3화THBS1기인갑기화재뇌막류발생、발전중적작용급기재뇌막류적조기진단、치료화예후평고중적개치.방법 수집산동대학제로의원1992지2005년수술치료적66례뇌막류환자적표본,기중단발성뇌막류30례,다발성뇌막류36례,대소유표본진행진단、조직학분형화분급,제취기인조DNA,이정상뇌조직주대조,용갑기화특이적PCR (MSP)법,검측종류조직표본중기인갑기화적정황,통계분석단발성뇌막류、다발성뇌막류급불동급별뇌막류지간갑기화솔차이.결과 30례단발성뇌막류중NF2、TIMP-3화THBS1기인갑기화솔분별시26.7％(8/30)、16.7％(5/30)화36.7％(11/30)；36례다발성뇌막류중3충기인적갑기화솔분별시30.6％(11/36)、22.2％(8/36)화22.2％(8/36),이정상뇌조직중3충기인균미검측도갑기화현상.Ⅰ～Ⅲ급뇌막류중단발화다발성자3충기인적갑기화솔차이균무통계학의의.이단발성、다발성뇌막류Ⅰ화Ⅱ、Ⅲ급간3충기인차이유통계학의의,이Ⅱ、Ⅲ급간차이무통계학의의.결론 NF2、TIMP-3화THBS1기인갑기화여비전형성화간변성뇌막류적발생、발전유관,야시뇌막류암변적중요원인,유조우뇌막류적림상진단,위뇌막류적조기발현제공방조.
Objective To explore the functions of NF2,TIMP-3 and THBS1 genes in the tumorigenesis or progression of meningiomas and analyze the values of these genes in early diagnosis,therapy and prognostic evaluation in meningiomas.Methods A total of 66 cases with histological sections of meningiomas,including solitary (SMs,n =30) and multiple meningiomas (MMs,n =36),were retrieved from our departmental archives.All cases were regrouped as benign,atypical and anaplastic (malignant) by hematoxylin & eosin staining according to the recently published WHO classification of nervous system tumors.Genomic DNA was extracted from tumor sections and methylation-specific polymerase chain reaction (MSP) performed to detect the CpG methylation status.Normal brain tissue was used as the control group.And then the differences of methylation rate between SMs and MMs tissues and among different subgroups were analyzed by statistical analyses.Results The results of methylation in different types of meningiomas demonstrated that the rates of NF2,TIMP-3 and THBS1 methylation were 26.7％ (8/30),16.7％ (5/30) and 36.7％ (11/30) in 30 SMs tissues and 30.6％ (11/36),22.2％ (8/36) and 22.2％ (8/36) in 36 MMs tissues respectively.But no aberrant methylation of NF2,TIMP-3 and THBS1 genes was found in normal brain tissue.No significant differences in three types of gene methylation rates existed between SMs and MMs in the Ⅰ-Ⅲ grade meningiomas.Nevertheless,there was great difference between grades Ⅰ,Ⅱ and Ⅲ in SMs and MMs while no significant difference was found between grades Ⅱ and Ⅲ.Conclusion The methylation of NF2,TIMP-3 and THBS1 is correlated with the tumorigenesis of meningiomas (grade Ⅱ and Ⅲ).As an important pathogenetic cause of meningiomas,it may be used as a clinical tool for an early diagnosis of meningiomas.