EZH2基因在卵巢癌发生发展中的作用及其临床病理意义  

Effects and Clinicopathologic Significance of EZH2 Gene in Tumorigenesis and Progression of Ovarian Carcinoma

作　　者：饶志跃[1] 杨国奋[2] 蔡木炎[3] 邓海霞[1] 廖奕佶[1] 谢丹[1] 

机构地区：[1]中山大学肿瘤防治中心研究部,广州市510060 [2]中山大学附属第一医院妇科 [3]中山大学肿瘤防治中心病理科

出　　处：《中国肿瘤临床》2010年第23期1321-1325,共5页Chinese Journal of Clinical Oncology

基　　金：国家自然科学基金(编号:30772334);广东省科技计划项目资助(编号:2004B35001004)~~

摘　　要：目的:探讨EZH2基因对卵巢癌细胞增殖和转移能力的影响,及其在卵巢癌组织中的表达与临床病理学意义。方法:运用EZH2小干扰RNA(siRNA)转染卵巢癌OVCAR-3细胞株,Western blot方法分析OVCAR-3细胞中EZH2的蛋白表达;MTT实验检测细胞增殖水平,Transwell小室实验检测细胞侵袭和转移能力。另外,应用RT-PCR和免疫组织化学法分别检测EZH2在卵巢癌组织中的mRNA和蛋白表达情况。结果:与阴性对照组相比,EZH2 siRNA能明显降低OVCAR-3细胞的EZH2蛋白表达,井显著抑制肿瘤细胞的增殖能力(P=0.032);转染EZH2 siRNA的OVCAR-3穿膜细胞数,在侵袭实验中,siEZH2组为29.3±5,与对照组(51±6.8)比较,差异有统计学意义(P=0.027);在迁移实验中,siEZH2组的迁移细胞数为51.6±7.7,显著低于对照组(72.3±11.7,P=0.036)。RT-PCR检测发现,卵巢癌组织中的EZH2 mRNA表达水平明显高于正常组织。在免疫组化实验中,61.0%的卵巢癌组织呈EZH2蛋白高表达,而且与卵巢癌的T分期、N分期以及FIGO分期显著正相关(P<0.05)。另外,单变量生存分析发现EZH2高表达与卵巢癌患者短生存期密切相关(P=0.007);多变量分析显示EZH2是卵巢癌的独立预后参数(P=0.047)。结论:EZH2在卵巢癌的发生与进展中发挥着重要的作用,而且EZH2高表达是卵巢癌患者预后不良的独立分子指标。Objective： To explore the effects of EZH2 gene on proliferation and metastasis of human ovarian cancer cell, and the mRNA and protein expression of EZH2 in ovarian carcinoma tissue, as well as its clinicopathologic significance. Methods： Small interfering RNA （siRNA） targeting EZH2 was applied to transiently knock down EZH2 in ovarian cancer OVCAR-3 cells, and then the protein expression of EZH2 in the OVCAR-3 cells was analyzed by Western blotting. The level of cell proliferation was determined using MTT assay, and the invasive and migrative ability were examined by Transwell assay. RT-PCR and immunohistochemistry was used to detect the EZH2 mRNA and protein status in ovarian cancer tissue, respectively. Results： Compared with the negative controls, EZH2 siRNA could effectively reduce the protein expression levels of EZH2 in OVCAR-3 cells and could significantly inhibit the proliferation of the cells （P= 0.032）. The number of invaded and migrated OVCAR-3 cells was significantly less in siEZH2 group than in siLuc group, respectively [invasion： （29.3±5） vs （51±6.8）, P=0.027; migration： （51.6±7.7）vs （72.3±11.7）, （P=0.036）]. The upregulated EZH2 mRNA expression was examined in ovarian cancer tissues compared with normal ovary. The immunohistochemistry for EZH2 high expression was detected in 61% of ovarian cancer tissues and its expression was positively correlated with T stage, lymph node metastasis and FIGO stage. In univariate analysis, a significant relationship between high expression of EZH2 and ohortened patient survival （P=0.007） was displayed. Multivariate analysis indicated EZH2 expression （P=0.047） was evaluated as an independent prognostic parameter. Conclusion： EZH2 plays an important role in the tumorigenesis and progression of ovarian carcinoma. High expression of EZH2 is an independent molecular marker of unfavourable prognosis in the patients with ovarian carcinoma.

关 键 词：卵巢癌 EZH2 RNA干扰预后 

分 类 号：R737.31[医药卫生—肿瘤]