RASAL1基因启动子甲基化及RAS活性与结肠癌临床病理的关系  

Clinical signif icance of RASAL1 promoter methylation and ras activity in colorectal carcinoma

作　　者：袁纯[1] 陆枫林[2] 陈洪[2] 

机构地区：[1]东南大学临床医学院,江苏省南京市210009 [2]东南大学附属中大医院消化科,江苏省南京市210009

出　　处：《世界华人消化杂志》2013年第4期341-345,共5页World Chinese Journal of Digestology

基　　金：江苏省自然科学基金资助项目;No.2008301~~

摘　　要：目的:检测RASAL1(ras GTPase-activatinglike protein 1)基因甲基化率及RAS活性在人结肠癌组织中的表达,探讨其与临床病理资料间的关系.方法:以40例结肠癌标本为研究对象,相应的正常组织标本为对照.甲基化特异性PCR(methylation-specific PCR,MSP)检测RASAL1启动子CpG岛甲基化状态,免疫共沉淀法检测RAS活性,分析肿瘤组织中RASAL1基因甲基化率及RAS活性与临床病理参数间的关系.结果:40例肿瘤组织中有26例检测出RASAL1基因甲基化(26/40,67.5%),对照组40例中有12例出现甲基化(12/40,30%),肿瘤组织甲基化率明显高于正常组织(P=0.0017).肿瘤组织中RAS活性的中位数为1.07,正常组织中RAS活性的中位数为0.52,P<0.001,差异有统计学意义.结肠癌组织中RASAL1基因的甲基化率、RAS活性与患者肿瘤分化程度、侵袭深度、淋巴结转移、TNM分期有统计学差异(均P<0.05).结论:RASAL1甲基化状态与RAS活性增加有关,可能在结肠癌的发生发展中起重要作用.抑制RASAL1甲基化及RAS活性,可能成为治疗结肠癌的新靶点.AIM：To detect RASAL1（ras GTPase-activatinglike protein 1） promoter methylation and ras activity in colorectal carcinoma（CRC） and to analyze their correlation with clinical and pathological parameters.METHODS：Methylation-specific PCR（MSP） was used to detect RASAL1 promoter methylation in forty CRC specimens and matched normal colorectal tissue specimens.Co-immunoprecipitation was used to detected ras activity in tumor and normal tissues.The correlation of RASAL1 promoter methylation and ras activity with clinical and pathological parameters was analyzed.RESULTS：RASAL1 promoter methylation was detected in 67.5%（26/40） of colorectal cancer tissues and in 30%（12/40） of normal tissues,and the positive rate of RASAL1 promoter methylation in tumor tissues was significantly higher than that in normal tissues（P=0.0017）.The median ras activity was significantly higher in colorectal cancer tissues than in normal tissues（1.07 vs 0.52,P0.001）.RASAL1 promoter methylation and ras activity were both positively correlated with degree of tumor differentiation,invasion depth,lymph node metastasis,and TNM stage（all P0.05）.CONCLUSION：High ras activity is related to RASAL1 promoter methylation,which may play an important role in the oncogenesis of CRC.RASAL1 methylation and ras activity may be novel therapeutic targets for CRC.

关 键 词：RASAL1 结肠癌 甲基化特异性PCR 免疫共沉淀 RAS活性 

分 类 号：R735.35[医药卫生—肿瘤]