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目的:探讨卵巢上皮癌中ING4基因启动子的甲基化状态及其临床意义。方法:收集2005年7月至2012年6月哈尔滨医科大学附属第一医院行全面分期手术并经病理检查确诊的150例卵巢上皮癌组织标本,并以同期因子宫肌瘤或子宫腺肌症行子宫全切除术或次全切除术并经病理检查确诊为正常卵巢组织的150例标本作为对照组。采用甲基化特异性PCR(MSP)技术检测卵巢上皮癌组织与正常卵巢组织中ING4基因启动子的甲基化状态,蛋白印迹法检测ING4蛋白的表达,并分析ING4基因启动子的甲基化状态与卵巢上皮癌临床病例特征的关系。结果:卵巢上皮癌组织中ING4基因启动子的甲基化阳性率为42.7%(64/150),明显高于正常卵巢组织(4%,6/150),差异有统计学意义(P<0.05)。ING4基因启动子甲基化阳性的卵巢上皮癌组织中ING4蛋白表达阴性或弱阳性;ING4基因启动子甲基化阴性的卵巢上皮癌和正常卵巢组织中ING4蛋白表达阳性;在64例ING4基因启动子甲基化的卵巢上皮癌组织中,ING4蛋白表达强度与ING4基因启动子的甲基化程度呈负相关(r=-0.435,P<0.05)。卵巢上皮癌组织中,ING4基因甲基化的阳性率随着手术病理分期和组织学分级的增加而增加(P<0.05);卵巢透明细胞癌(55.6%,10/18)和卵巢子宫内膜样癌(59.3%,16/27)中ING4基因甲基化的阳性率显著高于浆液性囊腺癌(33.9%,20/59)和粘液性囊腺癌(39.1%,18/46)(P<0.05);ING4基因启动子的甲基化状态与患者的年龄、有无腹水及淋巴结转移均无显著相关性(P>0.05)。结论:ING4基因启动子的甲基化可能促进了其在卵巢上皮癌组织中的表达失活,进而促进了卵巢上皮癌的生长和分化。
Objective: To investigate the methylation status of ING4 promoter in ovarian epithelial carcinoma and its clinical significance. Methods: From July 2005 to June 2012, the first affiliated hospital of Harbin Medical University and a total of 150 cases of ovarian epithelial cancer confirmed by pathological examination, and the same period due to uterine fibroids or adenomyosis Hysterectomy or subtotal resection and confirmed by pathological examination of 150 cases of normal ovarian tissue as a control group. Methylation-specific PCR (MSP) was used to detect the methylation status of ING4 promoter in epithelial ovarian cancer tissues and normal ovarian tissues. ING4 protein expression was detected by Western blotting. The methylation of ING4 promoter Relationship between clinical status and ovarian epithelial cancer clinical features. Results: The positive rate of ING4 promoter methylation in epithelial ovarian cancer was 42.7% (64/150), which was significantly higher than that in normal ovarian tissue (4%, 6/150) (P <0.05 ). ING4 promoter methylation-positive or negative epithelial ovarian cancer ING4 protein expression was negative or weakly positive; ING4 promoter methylation-negative epithelial ovarian cancer and normal ovarian tissue ING4 protein positive; in 64 cases of ING4 gene promoter In submethylated epithelial ovarian cancer, the expression of ING4 protein was negatively correlated with the methylation of ING4 promoter (r = -0.435, P <0.05). In ovarian epithelial carcinoma, the positive rate of ING4 methylation was increased with the increase of pathological staging and histological grade (P <0.05). The positive rate of ING4 methylation in ovarian clear cell carcinoma (55.6%, 10/18) and ovarian endometrium The positive rate of methylation of ING4 was significantly higher in patients with carcinoma (59.3%, 16/27) than in serous cystadenocarcinoma (33.9%, 20/59) and mucinous cystadenocarcinoma (39.1%, 18/46) P <0.05). The methylation status of ING4 promoter had no significant correlation with age, presence or absence of ascites and lymph node metastasis (P> 0.05). CONCLUSION: Methylation of ING4 promoter may promote its expression in ovarian epithelial cancer tissue inactivation, thereby promoting the growth and differentiation of epithelial ovarian cancer.