Quantitative detection of promoter hypermethylation in multiple genes in the serum of patients with colorectal cancer
Quantitative detection of promoter hypermethylation in multiple genes in the serum of patients with colorectal cancer
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DOI：
10.1111/j.1572-0241.2005.50412.x
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发表时间：
2005-10-01
影响因子：
9.8
通讯作者：
Sung, JJY
中科院分区：
文献类型：
--
作者：
Leung, WK;To, KF;Sung, JJY
目的：虽然启动子超甲基化是一种常见的人类结直肠癌，可以在血液中检测到的分子改变，我们测试的可行性定量检测异常的DNA甲基化在多个基因中的血清样品的结直肠癌patients.METHODS：治疗前的血清样品的49例结直肠癌患者和41个年龄匹配的对照正常结肠镜检查。APC中甲基化DNA的存在（腺瘤性结肠息肉病），hMLH 1（人MutL同源物1）和HLTF甲基化特异性定量PCR检测解旋酶样转录因子结果：癌症患者和对照组HLTF的甲基化血清DNA浓度有显著差异（p= 0.015）和hMLH 1（p= 0.0001）基因，但APC基因没有（p= 0.21）。总的来说，28例结直肠癌患者和4例对照者在至少一个标记物中检测到甲基化DNA，其灵敏度为57%，特异性为90%。所有两个甲基化标志物甲基化的患者均为晚期（III/IV期）癌症（p= 0.006），且至少一个甲基化标志物甲基化的患者生存概率较低（p= 0.08）。结论：定量检测血清中异常DNA甲基化可能是一种有前途的高通量方法，可用于结直肠癌的无创筛查和监测。
OBJECTIVES: While promoter hypermethylation is a common molecular alteration of human colorectal cancer that could be detected in the bloodstream, we tested the feasibility of quantitative detection of aberrant DNA methylation in multiple genes in the serum samples of colorectal cancer patients.METHODS: The pre-therapeutic serum samples of 49 colorectal cancer patients and 41 age-matched controls with normal colonoscopy were examined. The presence of methylated DNA in APC (adenomatous polyposis coli), hMLH1 (human MutL homolog 1), and HLTF (helicase-like transcription factor) was detected by quantitative methylation-specific PCR (MethyLight).RESULTS: There was a significant difference in the concentration of methylated serum DNA between cancer patients and controls for HLTF (p= 0.015) and hMLH1 (p= 0.0001) genes, but not for APC gene (p= 0.21). In total, 28 patients with colorectal cancer and 4 controls had methylated DNA detected in at least one marker, which gave a sensitivity of 57% and specificity of 90%. All patients with methylation in two methylation markers had advanced (stage III/IV) cancer (p= 0.006) and patients with methylation in at least one marker tended to have a lower probability of survival (p= 0.08).CONCLUSION: The quantitative detection of aberrant DNA methylation in serum may be a promising high-throughput approach for the noninvasive screening and monitoring of colorectal cancer.