Quantitative assessment of the diagnostic role of APC promoter methylation in non-small cell lung cancer.
Quantitative assessment of the diagnostic role of APC promoter methylation in non-small cell lung cancer.
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APC启动子甲基化对非小细胞肺癌诊断作用的定量评估
DOI：
10.1186/1868-7083-6-5
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发表时间：
2014-03-24
影响因子：
5.7
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Guo S;Tan L;Pu W;Wu J;Xu K;Wu J;Li Q;Ma Y;Xu J;Jin L;Wang J
背景：大肠腺瘤性息肉病（APC）已被报道是许多癌症的候选抑癌基因。然而，APC启动子甲基化在非小细胞肺癌（NSCLC）中的诊断作用仍不清楚。我们系统地整合了已发表的文章和DNA甲基化微阵列数据，以研究APC甲基化检测对NSCLC的诊断性能。从17项已发表的研究和TCGA NSCLC数据中收集了2259份NSCLC肿瘤样本和1,039份对照样本。在荟萃分析中评估了APC启动子甲基化与NSCLC之间的关联。结果：APC基因启动子区甲基化与非小细胞肺癌有显著相关性，随机效应模型的OR值为3.79（95%CI：2.22 ~ 6.45）。合并敏感性和特异性分别为0.548（95% CI：0.42 ~ 0.67，P < 0.0001）和0.776（95% CI：0.62 ~ 0.88，P < 0.0001）。五个CpG位点中的每一个在肺腺癌（Ad）中的预测（曲线下面积，AUC：0.71至0.73）比在肺鳞状细胞癌（Sc）中的预测（AUC：0.45至0.61）好得多。基于这五个CpG的逻辑预测模型的AUC对于Ad和Sc分别为0.73和0.60。综合分析显示，CpG位点的位置、异质性或自身对照以及样本中腺癌的比例是最显著的异质性来源。结论：APC基因启动子甲基化状态与NSCLC，尤其是腺癌密切相关。APC甲基化检测可用于肺腺癌的临床诊断。
Background:Adenomatous polyposis coli (APC) has been reported to be a candidate tumor suppressor in many cancers. However, the diagnostic role of APC promoter methylation in non-small cell lung cancer (NSCLC) remains unclear. We systematically integrated published articles and DNA methylation microarray data to investigate the diagnostic performance of the APC methylation test for NSCLC. Two thousand two hundred and fifty-nine NSCLC tumor samples and 1,039 controls were collected from 17 published studies and TCGA NSCLC data. The association between APC promoter methylation and NSCLC was evaluated in a meta-analysis. An independent DNA methylation microarray dataset from TCGA project, in which five CpG sites located in the promoter region of APC were involved, was used to validate the results of the meta-analysis.Results:A significant association was observed between APC promoter hypermethylation and NSCLC, with an aggregated odds ratio (OR) of 3.79 (95% CI: 2.22 to 6.45) in a random effects model. Pooled sensitivity and specificity were 0.548 (95% CI: 0.42 to 0.67, P < 0.0001) and 0.776 (95% CI: 0.62 to 0.88, P < 0.0001), respectively. Each of the five CpG sites was much better in prediction (area under the curve, AUC: 0.71 to 0.73) in lung adenocarcinoma (Ad) than in lung squamous cell carcinoma (Sc) (AUC: 0.45 to 0.61). The AUCs of the logistic prediction model based on these five CpGs were 0.73 and 0.60 for Ad and Sc, respectively. Integrated analysis indicated that CpG site location, heterogeneous or autogenous controls, and the proportion of adenocarcinoma in samples were the most significant heterogeneity sources.Conclusions:The methylation status of APC promoter was strongly associated with NSCLC, especially adenocarcinoma. The APC methylation test could be applied in the clinical diagnosis of lung adenocarcinoma.
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影响因子：
3.7
作者：
Gu J;Wen Y;Zhu S;Hua F;Zhao H;Xu H;You J;Sun L;Wang W;Chen J;Zhou Q
通讯作者：
Zhou Q
影响因子：
3.6
作者：
MIDGETTE, AS;STUKEL, TA;LITTENBERG, B
通讯作者：
LITTENBERG, B
DOI：
10.1073/pnas.1013224108
发表时间：
2011-03-15
影响因子：
11.1
作者：
Sproul, Duncan;Nestor, Colm;Ramsahoye, Bernard H.
通讯作者：
Ramsahoye, Bernard H.
DOI：
10.1348/000711010x522687
发表时间：
2011-02-01
影响因子：
2.6
作者：
Huizenga, Hilde M.;Visser, Ingmar;Dolan, Conor V.
通讯作者：
Dolan, Conor V.
DOI：
10.1016/0197-2456(86)90046-2
发表时间：
1986-09-01
期刊：
CONTROLLED CLINICAL TRIALS
影响因子：
--
作者：
DERSIMONIAN, R;LAIRD, N
通讯作者：
LAIRD, N