上皮性卵巢癌YAP核表达及肿瘤大小与预后的关联性研究
The correlation between YAP nuclear expression and tumor size with prognosis of epithelial ovarian cancer
李泽莲 1肖兰 1江玉 1季维雪 1陈颍 1杨媛媛 1曹云霞1
作者信息
- 1. 安徽医科大学第一附属医院妇产科,合肥 230022
- 折叠
摘要
目的 探讨上皮性卵巢癌(EOC)中YES相关蛋白(YAP)核表达与肿瘤大小及预后关系及YAP作用.方法 120例EOC患者组织标本为实验组,其中早期(Ⅰ+Ⅱ)和晚期(Ⅲ+Ⅳ)EOC分别为38和82例,30例选自子宫肌瘤患者的正常卵巢组织为对照组.免疫组织化学染色法检测YAP蛋白定位及表达,回顾性分析120例EOC患者临床资料,YAP核表达与EOC病理参数及患者预后相关性;不同初始细胞量培养EOC细胞系C13K及OV2008,使用免疫荧光及克隆形成实验分别检测Ki67表达及增殖情况;EOC细胞分别培养至汇合度为60％(低密度组)和90％(高密度组),q-PCR及Western blot分别检测YAP mRNA及蛋白在EOC细胞中表达.结果 YAP蛋白在EOC组织中胞核阳性表达率高于正常卵巢组织(P＜0.05);Ⅰ+Ⅱ期EOC肿瘤平均直径大于Ⅲ+Ⅳ期EOC(P＜0.01);YAP核高表达与病理学分级、临床分期、糖类抗原125(Ca125＞1 000 IU/ml)呈正相关,而与肿瘤大小呈负相关(P均＜0.05);生存分析提示肿瘤直径较小(＜10 cm)及YAP核高表达与EOC术后3年生存率呈负相关(P＜0.01).低密度组培养C13K及OV2008细胞克隆形成数目多,Ki67及YAP表达高(P＜0.01);敲低YAP表达可降低两种培养密度细胞的增殖能力(P＜0.05).结论 YAP核高表达及肿瘤直径小与EOC患者预后负相关,降低YAP核表达可使EOC细胞增殖能力减弱.
Abstract
Objective To investigate the correlation between Yes-associated protein(YAP)nuclear expression and tumor size with prognosis of patients with epithelial ovarian cancer(EOC)and to study the role of YAP in EOC.Methods 120 patients with EOC were selected as the experimental group,including 38 patients with early stage(Ⅰ+Ⅱ)EOC and 8 2 patients with advanced stage(Ⅲ+Ⅳ)EOC.3 0 normal ovarian tissues obtained from patients with uterine leiomyoma were enrolled as the control group.Immunohistochemical(IHC)assay was em-ployed to determine YAP expression and sub-location.The relationship between YAP expression and the pathologi-cal parameters of the 120 patients with EOC was analyzed,so as to the prognosis of these patients.EOC cells(C13K and OV2008)were cultured with varying initial cell volumes.Ki67 expression and cell proliferation were tested by immunofluorescence and cloning assay respectively.YAP expression at mRNA and protein levels were de-tected by q-PCR and Western blot respectively when the cell conference of EOC cells reached to low(60％)and high(90％)cell density.Results The YAP nuclear expression was significantly higher in the EOC group com-pared to the control group(P＜0.05).The average diameter of stage Ⅰ+Ⅱ EOC was larger than that of stage Ⅲ+Ⅳ EOC(P＜0.01).The high nuclear expression of YAP was positively associated with pathological grade,clinical stage and the level of Ca125＞1 000 IU/ml,while negatively correlated with tumor size(all P＜0.05).Survival analyses showed that smaller tumor size(＜10 cm)and higher YAP nuclear expression were negatively as-sociated with the 3-year overall survival rate of EOC patients(P＜0.01).C13K and OV2008 cells cultured in the low density group exhibited a high number of clone formation,high Ki67 and YAP expression(P＜0.01).The down-regulation of YAP expression could decrease the cell viability of EOC cells in the low-and high-density groups(P＜0.05).Conclusion Higher level of YAP nuclear expression and smaller tumour size are inversely associated with the clinical prognosis of patients with EOC.Inhibiting YAP nuclear expression leads to a decrease in the prolif-eration capacity of EOC cells.
关键词
YAP/上皮性卵巢癌/细胞增殖/肿瘤大小/细胞密度/预后Key words
YAP/epithelial ovarian cancer/cell proliferation/tumor size/cell density/prognosis引用本文复制引用
基金项目
国家自然科学基金青年基金(81603138)
出版年
2024
国家科技期刊平台
NSTL
万方数据