累积的启动子甲基化作为食管癌的潜在生物标志物。
Accumulated promoter methylation as a potential biomarker for esophageal cancer.
作者信息
Peng Xianzhen, Xue Hengchuan, Lü Lingshuang, Shi Peiyi, Wang Jianping, Wang Jianming
机构信息
Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Department of Public Health and Preventive Medicine, Kangda College of Nanjing Medical University, Lianyungang, 222000, China.
出版信息
Oncotarget. 2017 Jan 3;8(1):679-691. doi: 10.18632/oncotarget.13510.
We performed a two-stage molecular epidemiological study to explore DNA methylation profiles for potential biomarkers of esophageal squamous cell carcinoma (ESCC) in a Chinese population. Infinium Methylation 450K BeadChip was used to identify genes with differentially methylated CpG sites. Sixteen candidate genes were validated by sequencing 1160 CpG sites in their promoter regions using the Illumina MiSeq platform. When excluding sites with negative changes, 10 genes (BNIP3, BRCA1, CCND1, CDKN2A, HTATIP2, ITGAV, NFKB1, PIK3R1, PRDM16 and PTX3) showed significantly different methylation levels among cancer lesions, remote normal-appearing tissues, and healthy controls. PRDM16 had the highest diagnostic value with the AUC (95% CI) of 0.988 (0.965-1.000), followed by PIK3R1, with the AUC (95% CI) of 0.969 (0.928-1.000). In addition, the methylation status was higher in patients with advanced cancer stages. These results indicate that aberrant DNA methylation may be a potential biomarker for the diagnosis of ESCC.
我们开展了一项两阶段分子流行病学研究，以探索中国人群中食管鳞状细胞癌（ESCC）潜在生物标志物的DNA甲基化谱。采用Infinium甲基化450K芯片来识别具有差异甲基化CpG位点的基因。利用Illumina MiSeq平台对1160个位于其启动子区域的CpG位点进行测序，对16个候选基因进行验证。排除变化为负的位点后，10个基因（BNIP3、BRCA1、CCND1、CDKN2A、HTATIP2、ITGAV、NFKB1、PIK3R1、PRDM16和PTX3）在癌灶、远端外观正常组织和健康对照之间表现出显著不同的甲基化水平。PRDM16的诊断价值最高，AUC（95%CI）为0.988（0.965 - 1.000），其次是PIK3R1，AUC（95%CI）为0.969（0.928 - 1.000）。此外，癌症晚期患者的甲基化状态更高。这些结果表明，异常DNA甲基化可能是ESCC诊断的潜在生物标志物。
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