Ⅱ期散发性结直肠癌中CIMP与临床病理特征和预后的关系  

The relationship between CpG island methylator phenotype and the clinicopathological features and prognosis of stage Ⅱ sporadic colorectal cancer

作　　者：刘冰瑶 左腾[3] 任俊[3] 王鹏[3] 郭闻一[3] 汤志刚[3] 童卫东[1] 刘宝华[1] 付涛[1,3] 

机构地区：[1]第三军医大学大坪医院胃结直肠外科,重庆400042 [2]第三军医大学学员旅12营,重庆400038 [3]武汉大学人民医院胃肠外Ⅱ科,湖北武汉430060

出　　处：《实用肿瘤杂志》2016年第3期219-222,共4页Journal of Practical Oncology

基　　金：国家自然科学基金(81472289;81000898)

摘　　要：目的分析Ⅱ期散发性结直肠癌患者肿瘤CpG岛甲基化表型(CpG island methylator phenotype,CIMP)与临床病理因素和预后的关系,评价CIMP用于预后判断的可能价值。方法用甲基化特异性PCR技术分析135例Ⅱ期散发性结直肠癌中CACNA1G、IGF2、NEUROG1、RUNX3、SOCS1和MLH1基因甲基化水平,确定肿瘤CIMP状态;分析CIMP与MLH1基因甲基化、患者临床病理因素和预后的关系。结果 135例结直肠癌组织中31例(23.0%)为CIMP+,39例(28.9%)存在MLH1基因高甲基化。CIMP与MLH1基因甲基化呈正相关(P<0.01)。CIMP+多见于年龄≥60岁的患者(P=0.006)和右半结肠癌(P=0.018)。生存分析显示,CIMP+组患者总生存期较CIMP-组为短,但差异无统计学意义(P=0.100);无复发生存期两组间差异无统计学意义(P=0.973)。结论在Ⅱ期散发性结直肠癌中,CIMP与MLH1基因甲基化状态密切相关;CIMP+肿瘤常见于老年和右半结肠癌患者;CIMP可能有助于判断总生存期,但没有独立判断无复发生存期的意义。Objective To analyze the relationship between CpG island methylator phenotype（ CIMP） and the clinicopathological features and prognosis of stage Ⅱ sporadic colorectal cancer（ CRC） patients,and to evaluate the prognostic value of CIMP. Methods By using methylation specific PCR（ MSP）,we measured DNA methylation level of five carefully selected CIMP-specific loci（ CACNA1 G,IGF2,NEUROG1,RUNX3,SOCS1）,as well as MLH1 gene in 135 samples of stage Ⅱ sporadic CRC tumors. Furthermore,the impact of CIMP on MLH1 methylation,the clinicopathological features,and the prognosis was investigated. Results Among the 135 enrolled cases,thirty-one cases（ 23. 0%） were classified as CIMP ＋,and 39（ 28. 9%） cases showed MLH1 hypermethylation. CIMP was positively associated with high methylation of MLH1（ P〈0. 01）. CIMP ＋ was more frequently observed in age ≥60 patients（ P = 0. 006） and patients with right-side tumors（ P = 0. 018）. According to the survival analysis,patients in the CIMP ＋ group tended to have shorter overall survival time,compared with CIMP-group,although the difference was not statistically significant（ P = 0. 100）. There was no difference of relapse-free survival between the two groups（ P = 0. 973）. Conclusion MLH1 methylation is significantly associated with CIMP ＋ in stage Ⅱ sporadic CRCs. CIMP ＋ tumors are more often in elderly patients or patients with rightside tumors. CIMP may have prognostic value in determining the overall survival time,but not relapse-free survival.

关 键 词：结直肠肿瘤/病理学 结直肠肿瘤/遗传学 CpG岛/遗传学 DNA甲基化 表型 预后 

分 类 号：R735.34[医药卫生—肿瘤]