原发性肝癌RUNX3基因启动子区甲基化及mRNA表达及其意义  

Relationship between promoter methylation and mRNA expression of RUNX3 gene in human pri- mary hepatocellniar carcinoma and its significance

作　　者：江小杰[1] 李建国[1] 林志川[1] 

机构地区：[1]福建医科大学附属漳州市医院肝胆外科,福建漳州363000

出　　处：《中华实验外科杂志》2011年第10期1640-1642,共3页Chinese Journal of Experimental Surgery

基　　金：福建省自然科学基金资助项目（2009J01326）

摘　　要：目的观察原发性肝癌中人RUNT相关转录因子3（RUNX3）基因启动子甲基化及mRNA表达，探讨其甲基化与临床特征的关系。方法收集75例原发性肝癌患者的肿瘤标本及其癌旁组织、10例正常肝组织，应用甲基化特异性聚合酶链反应（MSP）测定RUNX3基因CpG岛甲基化状态，并采用实时定量聚合酶链反应（PCR）分析RUNX3基因在75例原发性肝癌中的表达水平及甲基化与肝癌临床特征的关系。结果75例肝癌组织中有34例（45．3％）存在RUNX3基因CpG岛的异常甲基化，癌旁组织中有7例（9．3％），而正常肝组织中未检测到RUNX3基因CpG岛的异常甲基化，RUNX3基因异常甲基化在肝癌组织、癌旁组织及正常组织中的发生率差异有统计学意义（χ2=29．18，P〈0．01）；75例原发性肝癌实时定量PCR分析有45例肝癌组织中存在RUNX3mRNA表达缺失或下调，其中60％（27／45）伴随启动子甲基化，即RUNX3mRNA表达下调与RUNX3基因甲基化密切相关（χ2=9．77，P〈0．01）；而肝癌组织非甲基化组RUNX3基因表达量高于甲基化组4倍以上；RUNX3基因CpG岛甲基化与患者肝硬化关系密切（χ2=5．07，P〈0．05）。结论原发性肝癌存在RUNX3基因CpG岛异常甲基化，CpG岛的甲基化可能是导致其基因表达降低的主要原因之一，并与患者肝硬化密切相关。Objective To determine the promoter methylation and mRNA expression of human runt-related transcription factor 3 （ RUNX3 ） gene in hepatoeellular carcinoma （HCC） and the relationship between the methylation and clinicopathological features. Methods The methylation status of 10 samples from human normal liver tissues, 75 samples from HCC and adjacent normal tissues, and its relationship with clinicopathological features were analyzed by methylation-specific polymerase chain reaction （MSP）. The expression of RUNX3 mRNA in all samples was detected. Results MSP results revealed that abnor- mal CpG island methylation of RUNX3 gene was found in 34 cases of HCC （45.3%） , 7 cases （9.3%） of adjacent normal tissues, and no abnormal CpG island methylation of RUNX3 was found in normal liver tissues （χ2 =29. 18,P 〈0. 01 ）. The down-regulation of RUNX3 mRNA was found in 45 out of 75 cases of HCC. Twenty-severn out of 45 （60%） HCC cases with lower expression of RUNX3 gene had the promoter hypermethylation. Statistically significant links were found between low RUNX3 mRNA levels and abnormal promoter methylation （χ2 = 9.77,P 〈 0.01 ）. The level of RUNX3 mRNA in HCC without methylation was over 4-fold higher than that in HCC with methylation. RUNX3 gene CpG island methylation was significantly correlated with cirrhosis （χ2 = 5.07, P 〈 0. 05 ）. Conclusion Promoter hypermethylation is an important mechanism for low expression of RUNX3 in HCC and is closely correlated to cirrhosis.

关 键 词：RUNX3基因 癌 肝细胞 甲基化 

分 类 号：R735.7[医药卫生—肿瘤]