Absolute quantitation of DNA methylation of 28 candidate genes in prostate cancer using pyrosequencing.
Absolute quantitation of DNA methylation of 28 candidate genes in prostate cancer using pyrosequencing.
复制标题
DOI：
10.3233/dma-2011-0790
复制
发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Lorincz AT
中科院分区：
文献类型：
--
作者：
Vasiljević N;Wu K;Brentnall AR;Kim DC;Thorat MA;Kudahetti SC;Mao X;Xue L;Yu Y;Shaw GL;Beltran L;Lu YJ;Berney DM;Cuzick J;Lorincz AT
DNA甲基化异常在前列腺癌的发生发展中起着重要作用，其定位可能为前列腺癌的诊断和风险评估提供生物标志物。我们使用焦磷酸测序（PSQ）方法定量并比较了48例PCa和29例良性前列腺增生（BPH）样本中28个候选基因的绝对甲基化水平，以确定具有诊断和预后潜力的基因。 与BPH相比，RARB、HIN 1、BCL 2、GSTP 1、CCND 2、EGFR 5、APC、RASSF 1A、MDR 1、NKX 2 -5、CDH 13、DPYS、PTGS 2、EDNRB、MAL、PDUM 4、HLA a、ESR 1和TIG 1在PCa中高度甲基化（p < 0.001），而SERPINB 5、CDH 1、TWIST 1、DAPK 1、THRB、MCAM、SLIT 2、CDKN 2a和SFN不是。高于21%的RARB甲基化完全区分PCa和BPH。基于SFN、SLIT 2和SERPINB 5的甲基化水平的分离区分了低和高Gleason评分癌症，例如SFN和SERPINB 5一起分别正确分类了81%和77%的高和低Gleason评分癌症。 包括CDH 1在内的几个基因先前报道为PCa中的甲基化标记，但在我们的研究中并未得到证实。年龄增长与基因甲基化正相关（p < 0.0001）。PCa中基因甲基化的精确定量测量似乎是有希望的，并且需要进一步验证诸如RARB、HIN 1、BCL 2、APC和GSTP 1等基因的诊断潜力以及SFN、SLIT 2和SERPINB 5的预后潜力。
Aberrant DNA methylation plays a pivotal role in carcinogenesis and its mapping is likely to provide biomarkers for improved diagnostic and risk assessment in prostate cancer (PCa). We quantified and compared absolute methylation levels among 28 candidate genes in 48 PCa and 29 benign prostate hyperplasia (BPH) samples using the pyrosequencing (PSQ) method to identify genes with diagnostic and prognostic potential. RARB, HIN1, BCL2, GSTP1, CCND2, EGFR5, APC, RASSF1A, MDR1, NKX2-5, CDH13, DPYS, PTGS2, EDNRB, MAL, PDLIM4, HLAa, ESR1 and TIG1 were highly methylated in PCa compared to BPH (p < 0.001), while SERPINB5, CDH1, TWIST1, DAPK1, THRB, MCAM, SLIT2, CDKN2a and SFN were not. RARB methylation above 21% completely distinguished PCa from BPH. Separation based on methylation level of SFN, SLIT2 and SERPINB5 distinguished low and high Gleason score cancers, e.g. SFN and SERPINB5 together correctly classified 81% and 77% of high and low Gleason score cancers respectively. Several genes including CDH1 previously reported as methylation markers in PCa were not confirmed in our study. Increasing age was positively associated with gene methylation (p < 0.0001). Accurate quantitative measurement of gene methylation in PCa appears promising and further validation of genes like RARB, HIN1, BCL2, APC and GSTP1 is warranted for diagnostic potential and SFN, SLIT2 and SERPINB5 for prognostic potential.