Yan Hongchao, Sun Jieyun
Department of Obstetrics and Gynecology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
Biomed Rep. 2013 May;1(3):375-378. doi: 10.3892/br.2013.86. Epub 2013 Mar 22.
WW domain-containing oxidoreductase (WWOX) is a newly identified tumor suppressor gene that is associated with abnormal DNA methylation. The aim of this study was to evaluate the methylation status of CpG islands in the WWOX gene promoter region in cases of epithelial ovarian cancer and explore the correlation between the methylation status of the WWOX gene CpG islands and clinicopathological indices in patients with epithelial ovarian cancer. The methylation status of the WWOX gene CpG island was evaluated by methylation-specific polymerase chain reaction (MSP) in 48 patients with epithelial ovarian cancer, 18 patients with borderline epithelial ovarian tumors, 26 patients with epithelial benign tumors and 33 patients with normal ovarian tissues. Results showed that the rates of CpG island methylation in the WWOX gene promoter region in epithelial ovarian cancer tissues, borderline ovarian tumor tissues and benign ovarian tumor tissues were 43.75, 26.32 and 3.84%, respectively. The WWOX gene CpG islands were not methylated in normal ovarian tissues. The rate of CpG island methylation in epithelial ovarian cancer tissues was higher than that of other ovarian tissues and these differences were found to be statistically significant (P<0.01). The rate of CpG island methylation in the WWOX gene promoter region in late-stage (stage III and IV) epithelial ovarian cancer tissues was higher than that of early-stage (stage I and II) epithelial ovarian cancer tissues, and these differences were found to be statistically significant (P<0.05). In conclusion, epithelial ovarian cancer tissues showed CpG island hypermethylation in the WWOX gene promoter region, which may be an important mechanism leading to WWOX gene inactivation. Atypical methylation of WWOX gene is associated with the formation and progression of epithelial ovarian cancer, rendering it a potentially important indicator in the early diagnosis and prognosis of epithelial ovarian cancer.
含WW结构域的氧化还原酶（WWOX）是一种新发现的抑癌基因，与DNA甲基化异常有关。本研究旨在评估上皮性卵巢癌患者中WWOX基因启动子区域CpG岛的甲基化状态，并探讨WWOX基因CpG岛甲基化状态与上皮性卵巢癌患者临床病理指标之间的相关性。采用甲基化特异性聚合酶链反应（MSP）对48例上皮性卵巢癌患者、18例交界性上皮性卵巢肿瘤患者、26例上皮性良性肿瘤患者和33例正常卵巢组织患者的WWOX基因CpG岛甲基化状态进行评估。结果显示，上皮性卵巢癌组织、交界性卵巢肿瘤组织和良性卵巢肿瘤组织中WWOX基因启动子区域CpG岛甲基化率分别为43.75%、26.32%和3.84%。正常卵巢组织中WWOX基因CpG岛未发生甲基化。上皮性卵巢癌组织中CpG岛甲基化率高于其他卵巢组织，差异有统计学意义（P<0.01）。晚期（Ⅲ期和Ⅳ期）上皮性卵巢癌组织中WWOX基因启动子区域CpG岛甲基化率高于早期（Ⅰ期和Ⅱ期）上皮性卵巢癌组织，差异有统计学意义（P<0.05）。综上所述，上皮性卵巢癌组织中WWOX基因启动子区域呈现CpG岛高甲基化，这可能是导致WWOX基因失活的重要机制。WWOX基因的异常甲基化与上皮性卵巢癌的发生和进展相关，使其成为上皮性卵巢癌早期诊断和预后的潜在重要指标。
