Department of Health Technology and Informatics, Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.
Cancer Epidemiol. 2013 Oct;37(5):708-13. doi: 10.1016/j.canep.2013.05.012. Epub 2013 Jun 20.
Promoter hypermethylation of tumor suppressor genes may serve as a promising biomarker for the diagnosis of cancer. Cell-free circulating DNA (cf-DNA) shares hypermethylation status with primary tumors. This study investigated promoter hypermethylation of five tumor suppressor genes as markers in the detection of nasopharyngeal carcinoma (NPC) in serum samples.
cf-DNA was extracted from serum collected from 40 NPC patients and 41 age- and sex-matched healthy subjects. The promoter hypermethylation status of the five genes (RASSF1, CDKN2A, DLEC1, DAPK1 and UCHL1) was assessed by methylation-specific PCR after sodium bisulfite conversion. Differences in the methylation status of these five genes between NPC patients and healthy subjects were compared.
The concentration of cf-DNA in the serum of NPC patients was significantly higher than that in normal controls. The five tumor suppressor genes - RASSF1, CDKN2A, DLEC1, DAPK1 and UCHL1 - were found to be methylated in 17.5%, 22.5%, 25.0%, 51.4% and 64.9% of patients, respectively. The combination of four-gene marker - CDKN2A, DLEC1, DAPK1 and UCHL1 - had the highest sensitivity and specificity in predicting NPC.
Screening DNA hypermethylation of tumor suppressor genes in serum was a promising approach for the diagnosis of NPC.
肿瘤抑制基因启动子的高甲基化可能成为癌症诊断的有前途的生物标志物。无细胞循环 DNA（cf-DNA）与原发肿瘤具有高甲基化状态。本研究调查了五个肿瘤抑制基因启动子的高甲基化作为血清样本中鼻咽癌（NPC）检测的标志物。
从 40 名 NPC 患者和 41 名年龄和性别匹配的健康受试者采集的血清中提取 cf-DNA。在亚硫酸氢盐转化后，通过甲基化特异性 PCR 评估五个基因（RASSF1、CDKN2A、DLEC1、DAPK1 和 UCHL1）的启动子高甲基化状态。比较 NPC 患者和健康受试者之间这五个基因的甲基化状态差异。
NPC 患者血清中 cf-DNA 的浓度明显高于正常对照组。五个肿瘤抑制基因 - RASSF1、CDKN2A、DLEC1、DAPK1 和 UCHL1 - 分别在 17.5%、22.5%、25.0%、51.4%和 64.9%的患者中发现甲基化。四基因标志物（CDKN2A、DLEC1、DAPK1 和 UCHL1）的组合在预测 NPC 方面具有最高的灵敏度和特异性。
筛查血清中肿瘤抑制基因的 DNA 高甲基化是诊断 NPC 的一种很有前途的方法。
