Woodson Karen, Hanson Jeffrey, Tangrea Joseph
Cancer Prevention Studies Branch, Center for Cancer Research, National Cancer Institute, 6116 Executive Blvd, MSC 8314, Bethesda, MD 20892 USA.
Cancer Lett. 2004 Mar 18;205(2):181-8. doi: 10.1016/j.canlet.2003.11.027.
Gene methylation is an important molecular event in prostate carcinogenesis that may have diagnostic and prognostic significance. We evaluated the methylation status of eight genes implicated in prostate carcinogenesis. DNA was extracted from archived paraffin-embedded tumor blocks from 90 prostate cancer patients. Gene methylation status of eight genes (GSTP1, RASSF1A, RARbeta2, CD44, EDNRB, E-cadherin, Annexin-2, and Caveolin-1) was determined using real-time methylation-sensitive PCR techniques. Differences in gene methylation among race, tumor grade and disease stage were evaluated by chi-square test. Of the eight genes, GSTP1, RASSF1A, and RARbeta2 methylation was highly prevalent across tumors (>60% for all three genes) whereas CD44, E-cadherin and EDNRB methylation was less prevalent (33, 24 and 29%, respectively). Annexin-2 and Caveolin-1 were not methylated in any of the tumors examined. Methylation of RARbeta2, CD44 and E-cadherin was correlated with tumor grade but not stage. Interestingly, methylation of EDNRB, a gene involved in angiogenesis, was correlated with stage of disease but not tumor grade. With the possible exception of CD44, we did not observe differences in gene methylation between racial categories for the genes under study. In summary, our data suggest that evaluation of the methylation of a panel of genes may have diagnostic and prognostic utility in prostate cancer.
基因甲基化是前列腺癌发生过程中的一个重要分子事件，可能具有诊断和预后意义。我们评估了八个与前列腺癌发生相关基因的甲基化状态。从90例前列腺癌患者存档的石蜡包埋肿瘤组织块中提取DNA。使用实时甲基化敏感PCR技术测定八个基因（GSTP1、RASSF1A、RARbeta2、CD44、EDNRB、E-钙黏蛋白、膜联蛋白-2和小窝蛋白-1）的基因甲基化状态。通过卡方检验评估种族、肿瘤分级和疾病分期之间基因甲基化的差异。在这八个基因中，GSTP1、RASSF1A和RARbeta2的甲基化在肿瘤中高度普遍（这三个基因均>60%），而CD44、E-钙黏蛋白和EDNRB的甲基化则不太普遍（分别为33%、24%和29%）。在所检测的任何肿瘤中，膜联蛋白-2和小窝蛋白-1均未发生甲基化。RARbeta2、CD44和E-钙黏蛋白的甲基化与肿瘤分级相关，但与分期无关。有趣的是，参与血管生成的基因EDNRB的甲基化与疾病分期相关，但与肿瘤分级无关。除了CD44可能例外，我们在所研究的基因中未观察到种族类别之间的基因甲基化差异。总之，我们的数据表明，评估一组基因的甲基化可能在前列腺癌中具有诊断和预后价值。
