CAJ | 학술논문

目的:研究卵巢上皮性癌组织中DAPK基因启动子甲基化及其蛋白表达在卵巢癌发生发展过程中的作用及意义.方法:应用甲基化特异性PCR(MSP)检测55例卵巢上皮性癌(恶性组)、25例卵巢交界性上皮性肿瘤(交界组)、30例卵巢良性上皮性肿瘤(良性组)、25例正常卵巢上皮组织(正常组)的石蜡包埋组织中DAPK基因启动子的甲基化情况.应用免疫组织化学链霉菌抗生物素蛋白-过氧化物酶连接(S-P)法检测上述蜡块组织中DAPK蛋白的表达情况.结果:DAPK启动子在正常组、良性组、交界组、恶性组的甲基化率分别为0(0/25)、6.7%(2/30)、16.0%(4/25)、47.3%(26/55),差异有统计学意义(P<0.001),恶性组的甲基化率高于其他三组;DAPK蛋白在正常组、良性组、交界组、恶性组的阳性表达率分别为96.0%(24/25)、90.0%(27/30)、48.0%(12/25)、30.9%(17/55),差异有统计学意义(P<0.001),恶性组、交界组的阳性表达率均低于正常组和良性组;DAPK基因启动子甲基化和DAPK蛋白表达呈负相关.结论:DAPK基因启动子甲基化导致基因沉默、失活,引起蛋白表达下调或缺失,并参与了卵巢上皮性癌的发生发展.
목적:연구란소상피성암조직중DAPK기인계동자갑기화급기단백표체재란소암발생발전과정중적작용급의의.방법:응용갑기화특이성PCR(MSP)검측55례란소상피성암(악성조)、25례란소교계성상피성종류(교계조)、30례란소량성상피성종류(량성조)、25례정상란소상피조직(정상조)적석사포매조직중DAPK기인계동자적갑기화정황.응용면역조직화학련매균항생물소단백-과양화물매련접(S-P)법검측상술사괴조직중DAPK단백적표체정황.결과:DAPK계동자재정상조、량성조、교계조、악성조적갑기화솔분별위0(0/25)、6.7%(2/30)、16.0%(4/25)、47.3%(26/55),차이유통계학의의(P<0.001),악성조적갑기화솔고우기타삼조;DAPK단백재정상조、량성조、교계조、악성조적양성표체솔분별위96.0%(24/25)、90.0%(27/30)、48.0%(12/25)、30.9%(17/55),차이유통계학의의(P<0.001),악성조、교계조적양성표체솔균저우정상조화량성조;DAPK기인계동자갑기화화DAPK단백표체정부상관.결론:DAPK기인계동자갑기화도치기인침묵、실활,인기단백표체하조혹결실,병삼여료란소상피성암적발생발전.
Objective:This study aimed to investigate the methylation and protein expression of death-associated protein kinase (DAPK) promoter in epithelial ovarian carcinoma (EOC). This study also aimed to evaluate the functions of DAPK methylation and protein expression in EOC development. Methods:Methylation-specific polymerase chain reaction was performed to detect DAPK promoter methylation in paraffin-embedded tissue specimens. The following specimens were examined:55 cases of EOC tissues (malignant group);25 borderline epithelial ovarian neoplasms (borderline group);30 cases of benign epithelial ovarian neoplasms (benign group);and 25 cases of normal epithelial ovarian tissue (normal group). Immunohistochemical streptavidin-peroxidase method was also performed to assess DAPK expression in the aforementioned specimens. Results:The rate of DAPK promoter methylation was 0%(0/25), 6.7%(2/30), 16.0%(4/25), and 47.3%(26/55) in normal, benign, borderline, and malignant groups, respectively. This rate was significantly higher in the malignant group than in the three groups (P<0.008 3). The rate of DAPK-positive protein expression was 96.0%(24/25), 90.0%(27/30), 48.0%(12/25), and 30.9%(17/55) in normal, benign, borderline, and malignant groups, respectively. This rate was significantly lower both in malignant and borderline groups than that in benign and normal groups, respectively (P<0.008 3). Thus, DAPK promoter methylation was negatively correlated with its protein expression. Conclusion:DAPK promoter methylation caused gene silencing and inactivity, thereby resulting in downregulation or loss of DAPK promoter protein expression, which contributed to oncogenesis and progression of EOCs.