Three Epigenetic Biomarkers, GDF15, TMEFF2, and VIM, Accurately Predict Bladder Cancer from DNA-Based Analyses of Urine Samples
Three Epigenetic Biomarkers, GDF15, TMEFF2, and VIM, Accurately Predict Bladder Cancer from DNA-Based Analyses of Urine Samples
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DOI：
10.1158/1078-0432.ccr-10-1312
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发表时间：
2010-12-01
影响因子：
11.5
通讯作者：
Lind, Guro E.
中科院分区：
文献类型：
--
作者：
Costa, Vera L.;Henrique, Rui;Lind, Guro E.
目的：为了鉴定一组表观遗传生物标志物用于准确检测尿沉渣中的膀胱癌（BlCa），实验设计：用5-氮杂-2 '脱氧胞苷和阿司他丁A处理的BlCa细胞系以及26个组织样品的基因表达微阵列分析用于鉴定BlCa的新甲基化候选物的列表。在来自51名BlCa患者和20名健康供体、19名肾癌患者和20名前列腺癌患者的4种BlCa细胞系、50种BlCa组织、20种正常膀胱粘膜（NBM）和尿沉淀物中定量候选基因的甲基化水平。结果：GDF 15、HSPA 2、TMEFF 2和Vim被确定为BlCa的表观遗传学生物标志物。膀胱癌组织中甲基化水平显著高于正常膀胱粘膜（P < 0.001），尿沉渣中甲基化水平仍保持癌特异性（P < 0.001）。包含GDF 15、TMEFF 2和Vim的甲基化组以100%的灵敏度和特异性正确鉴定了BlCa组织。在尿液样本中，该小组实现了94%的灵敏度和100%的特异性和0.975的曲线下面积。基因面板可以区分健康人和肾脏或前列腺癌患者的BlCa（敏感性，94%;特异性，90%）。结论：通过usingagenome-wideapproach，我们已经确定了一个生物标志物面板，允许早期和准确的非侵入性检测使用尿液样本的BlCa。Clin Cancer Res; 16（23）; 5842-51.（C）2010年AACR。
Purpose: To identify a panel of epigenetic biomarkers for accurate bladder cancer (BlCa) detection in urine sediments.Experimental Design: Gene expression microarray analysis of BlCa cell lines treated with 5-aza-2'deoxycytidine and trichostatin A as well as 26 tissue samples was used to identify a list of novel methylation candidates for BlCa. Methylation levels of candidate genes were quantified in 4 BlCa cell lines, 50 BlCa tissues, 20 normal bladder mucosas (NBM), and urine sediments from 51 BlCa patients and 20 healthy donors, 19 renal cancer patients, and 20 prostate cancer patients. Receiver operator characteristic curve analysis was used to assess the diagnostic performance of the gene panel.Results: GDF15, HSPA2, TMEFF2, and VIM were identified as epigenetic biomarkers for BlCa. The methylation levels were significantly higher in BlCa tissues than in NBM (P < 0.001) and the cancer specificity was retained in urine sediments (P < 0.001). A methylation panel comprising GDF15, TMEFF2, and VIM correctly identified BlCa tissues with 100% sensitivity and specificity. In urine samples, the panel achieved a sensitivity of 94% and specificity of 100% and an area under the curve of 0.975. The gene panel could discriminate BlCa from both healthy individuals and renal or prostate cancer patients (sensitivity, 94%; specificity, 90%).Conclusions: By usingagenome-wideapproach, we have identified a biomarker panel that allows for early and accurate noninvasive detection of BlCa using urine samples. Clin Cancer Res; 16(23); 5842-51. (C)2010 AACR.