Aberrant promoter methylation of CDH13 and MGMT genes is associated with clinicopathologic characteristics of primary non-small-cell lung carcinoma.
Aberrant promoter methylation of CDH13 and MGMT genes is associated with clinicopathologic characteristics of primary non-small-cell lung carcinoma.
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DOI：
10.1016/j.cllc.2011.11.003
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发表时间：
2012-07
影响因子：
3.6
通讯作者：
Nelson HH
中科院分区：
文献类型：
--
作者：
Kontic M;Stojsic J;Jovanovic D;Bunjevacki V;Ognjanovic S;Kuriger J;Puumala S;Nelson HH
系统性甲基化变化可能是肿瘤发展或预后的诊断标志物。在这里，我们研究了肺肿瘤相对于正常肺组织的基因甲基化之间的关系，以及是否可以在配对血液样本中检测到DNA甲基化变化。65例患者入组了一个单一机构的非小细胞肺癌（NSCLC）手术病例系列。使用亚硫酸氢盐焦磷酸测序，定量肺肿瘤、病理正常肺组织和来自登记病例的循环血液中的五个基因（RASSF1A、CDH13、MGMT、ESR1和DAPK）的CpG甲基化。与正常肺组织相比，肿瘤中的甲基化分析确定了CDH13、RASSF1A和DAPK基因的较高甲基化，而ESR1和MGMT甲基化在这些组织类型之间没有显著差异。然后，我们检查了这三个异常甲基化基因是否可以在血液中检测到。在肿瘤中观察到的甲基化差异并没有反映在匹配血液样本的甲基化状态中，这表明通过在基于血液的测试中分析这些基因来检测肺癌的可行性很低。最后，我们探讨了肿瘤甲基化是否与临床和人口统计学特征相关。组织学和性别与CDH13基因甲基化相关，而分期与MGMT甲基化相关。我们的研究结果显示，与正常肺相比，肺肿瘤中RASSF1A，CDH13和DAPK基因的甲基化程度更高。在NSCLC患者的血液样品中缺乏这些甲基化变化的反映表明它们不适合用于筛查测试。
Systemic methylation changes may be a diagnostic marker for tumor development or prognosis. Here, we investigate the relationship between gene methylation in lung tumors relative to normal lung tissue, and whether DNA methylation changes can be detected in paired blood samples. Sixty five patients were enrolled in a surgical case series of non-small cell lung cancer (NSCLC) at a single institution. Using bisulfite pyrosequencing, CpG methylation was quantified at five genes (RASSF1A, CDH13, MGMT, ESR1 and DAPK) in lung tumor, pathologically normal lung tissue, and circulating blood from enrolled cases. The analyses of methylation in tumors compared to normal lung tissue identified higher methylation of CDH13, RASSF1A, and DAPK genes, while ESR1 and MGMT methylation did not differ significantly between these tissue types. We then examined whether the three aberrantly methylated genes could be detected in blood. The difference in methylation observed in tumors was not reflected in methylation status of matching blood samples, indicating a low feasibility of detecting lung cancer by analyzing these genes in a blood-based test. Lastly we probed whether tumor methylation was associatied with clinical and demographic characteristics. Histology and gender were associated with methylation at the CDH13 gene, while stage was associated with methylation at MGMT. Our results show higher methylation of RASSF1A, CDH13, and DAPK genes in lung tumors compared to normal lung. The lack of reflection of these methylation changes in blood samples from patients with NSCLC indicate their poorly suitability for a screening test.
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影响因子：
9.7
作者：
Zhang, Youwei;Wang, Rui;Chen, Longbang
通讯作者：
Chen, Longbang
影响因子：
6.2
作者：
Kim, JS;Han, JH;Kim, DH
通讯作者：
Kim, DH
影响因子：
158.5
作者：
Brock, Malcolm V.;Hooker, Craig M.;Herman, James G.
通讯作者：
Herman, James G.
影响因子：
8
作者：
van Engeland, M;Roemen, GMJM;Herman, JG
通讯作者：
Herman, JG
影响因子：
11.2
作者：
van der Weyden, Louise;Adams, David J.
通讯作者：
Adams, David J.