hMLH1基因在结直肠癌中的甲基化水平及其预后意义

Methylation level of hMLH1 gene in colorectal cancer and its prognostic significance

目的:检测错配修复基因hMLH1在结直肠癌(colorectal cancer,CRC)中的甲基化水平并分析其预后意义。方法:调取有完整随访资料的68例CRC患者术后组织蜡块,所有患者均接受5-氟尿嘧啶(5-fluorouracil,5-Fu)及其衍生物为基础的辅助化疗4～6个周期,显微切割结合甲基化特异性聚合酶链反应(MSP)检测hMLH1基因启动子区域甲基化。结果:68例CRC组织中,16例(23.5%)检出hMLH1基因启动子甲基化,显著高于相应正常组织(3/68,4.4%,P=0.001)。尽管hMLH1基因异常甲基化与患者临床病理参数无关,生存分析表明hMLH1甲基化与无进展生存(progression-free survival,PFS)和总生存(overallsurvival,OS)获益有关(P值分别为0.039、0.045)。结论:hMLH1基因甲基化可望成为5-Fu辅助化疗CRC患者预后判断的新型分子标记。

Objective： To detect the promoter methylation status of hMLH1 gene in colorectal cancer（CRC） and evaluate its correlation with clinicopathological features and prognosis.Methods： The methylation status of hMLH1 gene was determined using manual microdissection followed by methylation-specific PCR（MSP） in 68 paired CRC specimens and adjacent normal tissues,all of the patients received 4～6 cycles of 5-fluorouracil（5-Fu） based adjuvant chemotherapy.Results： Methylation frequency of hMLH1 in cancerous tissue was 23.5%（16/68）,which was significantly higher than that in the corresponding normal tissue（3/68,4.4%,P = 0.001）.Although hMLH1 methylation was not associated with patients＇ clinicopathological features,Kaplan-Meier analysis showed the methylation state of hMLH1 predicted beneficial progression-free survival（PFS） and overall survival（OS） in CRC（P = 0.039 and P = 0.045,respectively）.Conclusion：hMLH1 gene methylation maybe a useful biomarker related to favourable prognosis in CRC patients who received 5-Fu based adjuvant chemotherapy.