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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 clinicopathological factors and prognosis in patients with stage Ⅱ sporadic colorectal cancer and to evaluate the possible value of CIMP in prognosis. Methods The methylation level of CACNA1G, IGF2, NEUROG1, RUNX3, SOCS1 and MLH1 in 135 patients with stage Ⅱ sporadic colorectal cancer was analyzed by methylation-specific PCR. The status of CIMP was determined. The methylation status of CIMP and MLH1 gene , The relationship between clinical and pathological factors and prognosis of patients. Results Thirty-one cases (23.0%) of 135 cases of colorectal cancer were CIMP +, and 39 cases (28.9%) had MLH1 hypermethylation. There was a positive correlation between CIMP and MLH1 methylation (P <0.01). CIMP + was more common in patients ≥60 years of age (P = 0.006) and right colon cancer (P = 0.018). Survival analysis showed that the overall survival of patients in CIMP + group was shorter than CIMP- group, but the difference was not statistically significant (P = 0.100). There was no significant difference between the two groups in recurrence-free survival (P = 0.973). Conclusions CIMP is closely related to the methylation status of MLH1 gene in sporadic Ⅱ colorectal cancer. CIMP + tumor is common in both elderly and right-sided colon cancer patients. CIMP may be helpful to determine the overall survival but not independent of relapse Meaning of survival.