Genome-wide methylation analysis shows similar patterns in Barrett's esophagus and esophageal adenocarcinoma.
Genome-wide methylation analysis shows similar patterns in Barrett's esophagus and esophageal adenocarcinoma.
复制标题
全基因组甲基化分析显示巴雷特食管和食管腺癌具有相似的模式。
DOI：
10.1093/carcin/bgt286
复制
发表时间：
2013
期刊：
影响因子：
4.7
通讯作者：
Wu,Xifeng
中科院分区：
文献类型：
--
作者：
Xu,Enping;Gu,Jian;Hawk,ErnestT;Wang,KennethK;Lai,Maode;Huang,Maosheng;Ajani,Jaffer;Wu,Xifeng
巴雷特食道(BE)是食管腺癌(EAC)的先兆。为了确定与食道癌发生有关的新的肿瘤抑制因子和BE恶性进展的潜在生物标志物，我们对BE和EAC组织进行了全基因组甲基化分析。应用Illumina公司的Infinium Human Megylation27芯片芯片，我们检测了94例正常食管瘤、77例BE和117例EAC组织中27578个CpG位点的甲基化状态。BE和EAC组织中CpG岛的甲基化水平高于NE组织，而CpG岛外的CpG位点甲基化水平低于NE组织。系统聚类分析显示NE组织与BE和EAC组织有很好的分离；但BE和EAC组织的聚集性不太清楚，这表明甲基化发生在EAC进展的早期。我们证实了许多已报道的高甲基化基因，并在BE和EAC组织中发现了大量的新的高甲基化基因，特别是编码ADAM(A去整合素和金属蛋白酶)肽酶蛋白、钙粘附素和原钙粘附素的基因，以及钾电压门控通道。通路分析表明，高甲基化基因的许多通道和转运蛋白活性都得到了丰富。我们使用焦磷酸测序来验证选定的候选基因，并发现阵列和焦测序数据之间有很高的相关性(每个验证基因的Rho>；0.8)。差异甲基化的基因和途径可能为BE的发生和发展提供生物学见解，成为预测和早期发现EAC的潜在生物标志物。
Barrett’s esophagus (BE) is a precursor of esophageal adenocarcinoma (EAC). To identify novel tumor suppressors involved in esophageal carcinogenesis and potential biomarkers for the malignant progression of BE, we performed a genome-wide methylation profiling of BE and EAC tissues. Using Illumina’s Infinium HumanMethylation27 BeadChip microarray, we examined the methylation status of 27 578 CpG sites in 94 normal esophageal (NE), 77 BE and 117 EAC tissue samples. The overall methylation of CpG sites within the CpG islands was higher, but outside of the CpG islands was lower in BE and EAC tissues than in NE tissues. Hierarchical clustering analysis showed an excellent separation of NE tissues from BE and EAC tissues; however, the clustering of BE and EAC tissues was less clear, suggesting that methylation occurs early during the progression of EAC. We confirmed many previously reported hypermethylated genes and identified a large number of novel hypermethylated genes in BE and EAC tissues, particularly genes encoding ADAM (A Disintegrin And Metalloproteinase) peptidase proteins, cadherins and protocadherins, and potassium voltage-gated channels. Pathway analysis showed that a number of channel and transporter activities were enriched for hypermethylated genes. We used pyrosequencing to validate selected candidate genes and found high correlations between the array and pyrosequencing data (rho > 0.8 for each validated gene). The differentially methylated genes and pathways may provide biological insights into the development and progression of BE and become potential biomarkers for the prediction and early detection of EAC.