Early involvement of death-associated protein kinase promoter hypermethylation in the carcinogenesis of Barrett's esophageal adenocarcinoma and its association with clinical progression
Early involvement of death-associated protein kinase promoter hypermethylation in the carcinogenesis of Barrett's esophageal adenocarcinoma and its association with clinical progression
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DOI：
10.1593/neo.06802
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发表时间：
2007-03-01
期刊：
影响因子：
4.8
通讯作者：
Schneider-Stock, Regine
中科院分区：
文献类型：
--
作者：
Kuester, Doerthe;Dar, Altaf A.;Schneider-Stock, Regine
食管Barrett's腺癌（BA）的发生发展是一个多阶段的过程，与启动子CpG岛高甲基化导致抑癌基因转录沉默有关。在这项研究中，我们探讨了启动子超甲基化和蛋白表达的促凋亡死亡相关蛋白激酶（DAPK）在多步骤巴雷特的致癌级联反应。通过甲基化特异性聚合酶链反应和免疫组化分析了61例患者的早期BA和癌前病变配对样本。对于临床病理标志物和蛋白质表达的关联，对另外66个晚期肿瘤阶段的BA进行免疫组织化学组织微阵列分析。在20%的正常粘膜、50%的Barrett's化生、53%的异型增生和60%的腺癌中检测到DAPK启动子的高甲基化，并导致DAPK蛋白表达显著降低（P
Esophageal Barrett's adenocarcinoma ( BA) develops through a multistage process, which is associated with the transcriptional silencing of tumor-suppressor genes by promoter CpG island hypermethylation. In this study, we explored the promoter hypermethylation and protein expression of proapoptotic death-associated protein kinase ( DAPK) during the multistep Barrett's carcinogenesis cascade. Early BA and paired samples of premalignant lesions of 61 patients were analyzed by methylation-specific polymerase chain reaction and immunohistochemistry. For the association of clinicopathological markers and protein expression, an immunohistochemical tissue microarray analysis of 66 additional BAs of advanced tumor stages was performed. Hypermethylation of DAPK promoter was detected in 20% of normal mucosa, 50% of Barrett's metaplasia, 53% of dysplasia, and 60% of adenocarcinomas, and resulted in a marked decrease in DAPK protein expression ( P