Detection of bladder cancer using novel DNA methylation biomarkers in urine sediments.
Detection of bladder cancer using novel DNA methylation biomarkers in urine sediments.
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DOI：
10.1158/1055-9965.epi-11-0067
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发表时间：
2011-07
期刊：
影响因子：
--
通讯作者：
Issa JP
中科院分区：
文献类型：
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作者：
Chung W;Bondaruk J;Jelinek J;Lotan Y;Liang S;Czerniak B;Issa JP
膀胱癌仍然是一种致命的恶性肿瘤，如果及早发现是可以治愈的。DNA高甲基化是癌症中一种常见的表观遗传学异常，可作为疾病活动的标志。我们从DNA芯片和亚硫酸氢盐焦糖测序检测到的膀胱癌最常见的高甲基化基因中筛选出10个新的候选基因，并将其应用于尿沉渣中膀胱癌的检测。我们用定量甲基化特异性实时聚合酶链式反应(QMSP)分析了128例膀胱癌患者和110例年龄匹配的对照组尿沉渣中候选基因的DNA甲基化情况。基于多基因预测模型，我们发现6个甲基化标志物(MYO3A、CA10、SOX11、NKX6-2、PENK和DBC1)最有希望检测膀胱癌。4个基因(MYO3A、CA10、NKX6-2和Dbc1或Sox11)诊断膀胱癌的敏感性和特异性分别为81%和97%，而5个基因(MYO3A、CA10、NKX6-2、Dbc1和Sox11或PENK)对膀胱癌的诊断敏感性和特异性分别为85%和95%(AUC=0.939)。按肿瘤侵袭性进行分析，非肌肉浸润性肿瘤(PTA、Tis和PT1)的检出率为47/58(81%)，肌肉浸润性肿瘤(T2、T3和T4)的检出率为62/70(90%)。QMSP分析的这一生物标志物组合可能有助于早期发现尿沉渣中的膀胱肿瘤，并具有较高的准确性。生物标记物小组值得在大量控制良好的预期收集的样本集中进行验证。
Bladder cancer remains a lethal malignancy that can be cured if detected early. DNA hypermethylation is a common epigenetic abnormality in cancer that may serve as a marker of disease activity. We selected 10 novel candidate genes from the most frequently hypermethylated genes detected by DNA microarray and bisulfite pyrosequencing of bladder cancers and applied them to detect bladder cancer in urine sediments. We analyzed DNA methylation in the candidate genes by quantitative methylation specific real time PCR (qMSP) to detect bladder cancer in urine sediments from 128 bladder cancer patients and 110 age-matched control subjects. Based on a multi-gene predictive model, we discovered 6 methylation markers (MYO3A, CA10, SOX11, NKX6-2, PENK and DBC1) as most promising for detecting bladder cancer. A panel of 4 genes (MYO3A, CA10, NKX6-2 and DBC1 or SOX11) had 81 % sensitivity and 97 % specificity, while a panel of 5 genes (MYO3A, CA10, NKX6-2, DBC1 and SOX11 or PENK) had 85 % sensitivity and 95 % specificity for detection of bladder cancer (AUC=0.939). Analyzing the data by cancer invasiveness, detection rate was 47 out of 58 (81 %) in non-muscle invasive tumors (pTa, Tis and pT1) and 62 out of 70 (90 %) in muscle invasive tumors (T2, T3 and T4). This biomarker panel analyzed by qMSP may help the early detection of bladder tumors in urine sediments with high accuracy. The panel of biomarker deserves validation in a large well-controlled prospectively collected sample set.