EFEMP1 as a Novel DNA Methylation Marker for Prostate Cancer: Array-Based DNA Methylation and Expression Profiling
EFEMP1 as a Novel DNA Methylation Marker for Prostate Cancer: Array-Based DNA Methylation and Expression Profiling
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DOI：
10.1158/1078-0432.ccr-10-2817
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发表时间：
2011-07-01
影响因子：
11.5
通讯作者：
Kim, Wun-Jae
中科院分区：
文献类型：
--
作者：
Kim, Yong-June;Yoon, Hyung-Yoon;Kim, Wun-Jae
目的：DNA甲基化异常与多种人类癌症有关。本研究的目的是通过微阵列分析寻找前列腺癌(PCa)中新的甲基化标志物，并测试这些标志物是否能够区分正常细胞和前列腺癌细胞。实验设计：利用一组前列腺癌细胞系和一个对照的正常前列腺细胞系，进行基于基因芯片的DNA甲基化和基因表达谱分析。通过实时逆转录-聚合酶链式反应、亚硫酸氢盐测序分析和去甲基化试剂处理，证实了前列腺细胞系候选基因的甲基化状态。对203例前列腺癌(PCa)组织和97例良性前列腺增生症(BPH)组织进行DNA甲基化和基因表达分析。结果：含有表皮生长因子的纤维蛋白样细胞外基质蛋白1(EFEMP1)被确定为前列腺癌的主要候选甲基化标志物。EFEMP1基因在良性前列腺增生症患者组织中的表达水平显著高于PCa患者(P<；0.001)。EFEMP1甲基化状态对前列腺癌和良性前列腺增生症鉴别诊断的敏感性和特异性分别为95.3%(101/106)和86.6%(84/97)。从GEO数据集，我们证实了EFEMP1在PCa和BPH中的表达水平显著不同。结论：DNA甲基化图谱的全基因组特征能够识别EFEMP1在PCa中的异常甲基化模式。EFEMP1可能是检测前列腺癌的有用指标。临床癌症资源；17(13)；4523-30。(C)2011年AACR。
Purpose: Abnormal DNA methylation is associated with many human cancers. The aim of the present study was to identify novel methylation markers in prostate cancer (PCa) by microarray analysis and to test whether these markers could discriminate normal and PCa cells.Experimental Design: Microarray-based DNA methylation and gene expression profiling was carried out using a panel of PCa cell lines and a control normal prostate cell line. The methylation status of candidate genes in prostate cell lines was confirmed by real-time reverse transcriptase-PCR, bisulfite sequencing analysis, and treatment with a demethylation agent. DNA methylation and gene expression analysis in 203 human prostate specimens, including 106 PCa and 97 benign prostate hyperplasia (BPH), were carried out. Further validation using microarray gene expression data from the Gene Expression Omnibus (GEO) was carried out.Results: Epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) was identified as a lead candidate methylation marker for PCa. The gene expression level of EFEMP1 was significantly higher in tissue samples from patients with BPH than in those with PCa (P < 0.001). The sensitivity and specificity of EFEMP1 methylation status in discriminating between PCa and BPH reached 95.3% (101 of 106) and 86.6% (84 of 97), respectively. From the GEO data set, we confirmed that the expression level of EFEMP1 was significantly different between PCa and BPH.Conclusion: Genome-wide characterization of DNA methylation profiles enabled the identification of EFEMP1 aberrant methylation patterns in PCa. EFEMP1 might be a useful indicator for the detection of PCa. Clin Cancer Res; 17(13); 4523-30. (C) 2011 AACR.