hMLH1基因在结直肠癌中的甲基化水平及其预后意义
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Methylation level of hMLH1 gene in colorectal cancer and its prognostic significance
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    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(overall survival,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-

    Abstract:

    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.

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朱 卉,汪 竹,袁 昕,焦南林,张有为,童建东. hMLH1基因在结直肠癌中的甲基化水平及其预后意义[J].南京医科大学学报(自然科学版),2012,(3):391-394

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  • 收稿日期:2011-08-09
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