雌激素受体相关受体亚型在卵巢癌中的表达及其与预后的关系

Role of estrogen receptor-related receptors α, β and γ in ovarian cancer cells

目的探讨雌激素受体相关受体(ERRs)亚型α、β、γ在卵巢癌中的表达及其与预后的关系。方法激光共聚焦显微镜观察ERRα蛋白在卵巢癌细胞株SKOV3和OVCAR3细胞内的定位。RT-PCR技术检测33份卵巢癌组织以及12份正常卵巢组织中3种ERRs亚型的mRNA表达,并结合临床病理指标分析其预后情况。结果ERRα蛋白主要分布于SKOV3和OVCAR3细胞的细胞核内。卵巢癌组织中ERRαmRNA的阳性表达率(58%)和ERRγmRNA的阳性表达率(48%)显著高于正常卵巢组织(分别为17%和33%,P<0.05);ERRβmRNA的阳性表达率在卵巢癌组织和正常卵巢组织中都很低(分别为9%和0),两者比较,差异无统计学意义(P=0.795)。ERRαmRNA的阳性表达与卵巢癌的手术病理分期(r=0.639,P=0.017)、病理分级(r=0.520,P=0.022)呈正相关。ERRαmRNA阳性表达的卵巢癌患者,其中位数整体生存时间(19.0个月)明显短于ERRαmRNA阴性表达患者(31.5个月,P=0.015),但两者间的无瘤生存时间(分别为12.6和14.5个月)比较,差异无统计学意义(P=0.820);ERRγmRNA阳性表达患者的中位数无瘤生存时间(18.0个月)显著长于ERRγmRNA阴性表达患者(13.5个月,P=0.020),但两者间中位数整体生存时间(分别为23.4和19.6个月)比较,差异无统计学意义(P=0.093)。结论ERRα蛋白主要表达于卵巢癌细胞核内。ERRαmRNA高表达与卵巢癌患者的预后差有关,而ERRγmRNA高表达可能提示患者预后较好。

Objective To investigate the role of human estrogen receptor-related receptors （ERRs） in ovarian cancer. Methods A green fluorescent protein （GFP） reporter plasmid of ERRα was constructed and transfected into ovarian cancer cell lines SKOV3 and OVCAR3. RT-PCR was used to analyze the expression of ERRα, ERRβ, and ERRγ mRNA in 33 primary ovarian cancer samples and 12 normal ovarian epithelial cells. Progression-free survival time and overall survival time of patients with different expression of ERRs were analyzed by Kaplan-Meier method. Results GFP-ERRα fusion protein showed ERRα expressed in the ovarian cancer cell nucleus. Expressions of the ERRα and ERRγ, were increased in the ovariancan cers （58% and 48% ） compared with the normal ovarian tissues （P 〈 0. 05 ）; ERRβ was weakly expressed in the ovarian cancer （9%） as well as in the normal tissues （0）. Expression of ERRα was positively correlated with the International Federation of Gynecology and Obstetrics （ FIGO ） stage （ r =0. 639, P =0. 017） and cell grading（r =0. 520, P =0. 022）. Survival analysis showed that ERRα positive group had a poorer overall survival （ 19. 0 months vs. 31.5 months, P 〈 0. 05 ） and ERRγ positive group had a longer progression-free survival （ 18.0 months vs. 13.5 months, P 〈 0. 05）. Conclusions ERRα chiefly expresses in the cell nucleus. ERRα and ERRγ may play important roles in ovarian cancer.