Huang Jin, Wang Guo, Tang Jie, Zhuang Wei, Wang Li-Ping, Liou Yu-Ligh, Liu Ying-Zi, Zhou Hong-Hao, Zhu Yuan-Shan
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, Hunan, China.
Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, Hunan, China.
Int J Environ Res Public Health. 2017 Feb 22;14(2):216. doi: 10.3390/ijerph14020216.
Hypermethylation of specific gene promoters is an important mechanism of carcinogenesis. A high frequency of promoter methylation of and genes has been detected in cervical cancer. In the present study, we investigated the methylation status of and genes in esophageal squamous cell carcinoma (ESCC) tissues. Tumor and paracancerous tissues were obtained from 14 ESCC patients. Genomic DNA was extracted from both tumor and paracancerous tissues, and the concentration of DNA were determined. DNA methylation analysis of and genes was carried out using quantitative methylation-specific PCR. To assess the diagnostic performance of the two methylated genes for cancer detection, receiver operating characteristic (ROC) curves were generated. Sensitivities and specificities were tested at cut-offs obtained from the ROC curves. The methylation levels of both and genes were significantly higher in tumor tissues compared to non-tumor paracancerous tissues. The methylation rates of and in ESCC tumor and paracancerous tissues were 100% and 21.4% ( = 0.006), 85.7% and 0% ( < 0.001), respectively. The sensitivities and specificities of and methylation for the detection of cancer were 100% and 85.7%, and 78.6% and 100%, respectively. The DNA methylation levels and frequencies of and genes were markedly higher in ESCC tumor tissues compared to those in paracancerous tissues. Moreover, the conclusions were verified by using The Cancer Genome Atlas (TCGA) datasets. DNA methylation status of these two genes showed a relatively good sensitivity and specificity for the detection of ESCC tumors. This data suggests that DNA methylation testing holds a great promise for ESCC screening and warrants further prospective population-based studies.
特定基因启动子的高甲基化是致癌的重要机制。在宫颈癌中已检测到 和 基因启动子甲基化的高频率。在本研究中，我们调查了食管鳞状细胞癌（ESCC）组织中 和 基因的甲基化状态。从14例ESCC患者获取肿瘤组织和癌旁组织。从肿瘤组织和癌旁组织中提取基因组DNA，并测定DNA浓度。使用定量甲基化特异性PCR对 和 基因进行DNA甲基化分析。为评估这两个甲基化基因用于癌症检测的诊断性能，绘制了受试者工作特征（ROC）曲线。在从ROC曲线获得的临界值处测试敏感性和特异性。与非肿瘤癌旁组织相比，肿瘤组织中 和 基因的甲基化水平均显著更高。ESCC肿瘤组织和癌旁组织中 和 的甲基化率分别为100%和21.4%（ = 0.006）、85.7%和0%（ < 0.001）。 和 甲基化用于癌症检测的敏感性和特异性分别为100%和85.7%，以及78.6%和100%。与癌旁组织相比，ESCC肿瘤组织中 和 基因的DNA甲基化水平和频率明显更高。此外，通过使用癌症基因组图谱（TCGA）数据集验证了这些结论。这两个基因的DNA甲基化状态对ESCC肿瘤的检测显示出相对较好的敏感性和特异性。该数据表明DNA甲基化检测在ESCC筛查方面具有很大前景，值得进一步开展基于人群的前瞻性研究。
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