摘要
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.
出处
《南京医科大学学报(自然科学版)》
CAS
CSCD
北大核心
2012年第3期391-394,共4页
Journal of Nanjing Medical University(Natural Sciences)