非小细胞肺癌INK4a和ARF基因甲基化与其蛋白共表达关系的探讨  

The Relationship between INK4a/ARF Genes Methylation and Proteins Co-expression in Non-small Cell Lung Cancer

作　　者：高丽莉[1] 胡义德[1] 李军果[1] 谢启超[1] 孙恒文[1] 胡中华[1] 

机构地区：[1]第三军医大学附属新桥医院全军肿瘤中心,重庆市400037

出　　处：《中国肿瘤临床》2006年第3期130-133,共4页Chinese Journal of Clinical Oncology

基　　金：国家自然科学基金(编号:30170293);重庆市自然科学基金项目资助(2005)

摘　　要：目的:分析INK4a和ARF基因启动子甲基化与其蛋白共表达之间的关系。方法:选择前期实验中p14ARF和p16INK4a蛋白共表达阴性的非小细胞肺癌(NSCLC)患者35例,共表达阳性的NSCLC患者20例作为研究对象,分别称为(p14+p16)阴性组和(p14+p16)阳性组。运用甲基化特异性PCR(MSP)方法对两组患者癌组织INK4a和ARF基因启动子的甲基化状态进行检测。结果:(p14+p16)阴性组有18例发生INK4a基因甲基化,(p14+p16)阳性组有2例发生INK4a基因甲基化,两组差异有显著意义(P<0.01)。(p14+p16)阴性组有8例发生ARF基因启动子甲基化,(p14+p16)阳性组有2例发生ARF基因启动子甲基化,两组差异无显著意义(P>0.05)。INK4a和ARF基因异常甲基化相互之间无显著相关性(P>0.05)。结论:NSCLC患者肺癌组织INK4a基因甲基化是导致p16INK4a蛋白表达阴性的重要机制;INK4a和ARF基因甲基化可能是相对独立的事件。Objective： To study the relationship between INK4a/ARF genes methylation and proteins co-expression in non-small cell lung cancer. Methods： Sections were obtained from previous 10%-formalin-fixed and paraffin-embedded tissues, including 35 NSCLC samples with p14^ARt and p16^INK4a negative co-expression and 20 NSCLC samples with p14ARt and p16^INK4a positive co-expression. These samples were divided into two groups and were named as the （p14＋p16） negative group and the （p14＋p16） positive group respectively. The 5CpG islands methylation state of tumor suppressor gene INK4a/ARF was determined by methylation specific polymerase chain reaction （MSP）. Results： The hypermethylation rate of INK4a gene was 51.4 %（18/35） in （p14＋p16） negative group, but 10 %（2/20） in （p14＋p16） positive group. There was a significant difference between the two groups （P=0.002）. The hypermethylation frequency of ARF gene was 22.8 %（8/35） in the （p14＋p16） negative group, and was 10 %（2/20） in the （p14＋p16）positive group. There was no significant difference between the two groups（P= 0.409） and was no obviously correlation between INK4a gene hypermethylation and ARF gene hypermethylation. Condusion： INK4a gene hypermethylation is one of the important mechanisms that results in p16^INK4a proteins negative expression in NSCLC. The hypermethylation of INK4a and ARF genes are independent each other.

关 键 词：非小细胞肺癌 INK4a基因 ARF基因 甲基化 甲基化特异性PCR 

分 类 号：R734.2[医药卫生—肿瘤]