上皮膜蛋白1在上皮性卵巢癌顺铂耐药中的作用及意义  

Role and significance of EMP1 in cisplatin resistance of epithelial ovarian cancer

作　　者：曾庆松[1,2,3] 彭笑 何文容 王晓雯[1] 陈克明[1,3] 易村犍[1,3] ZENG Qingsong;PENG Xiao;HE Wenrong;WANG Xiaowen;CHEN Keming;YI Cunjian(The First Affiliated Hospital of Yangtze University,Jingzhou Hubei 434000,China;Health Science Center,Yangtze University,Jingzhou Hubei,430023,China;Clinical Medical Research Center for Personalized Diagnosis and Treatment of Cancer,430023,China)

机构地区：[1]长江大学附属第一医院妇产科,湖北荆州434000 [2]长江大学医学部,湖北荆州434023 [3]湖北省肿瘤个体化诊疗临床医学研究中心,湖北荆州434023

出　　处：《中国妇产科临床杂志》2024年第2期136-140,共5页Chinese Journal of Clinical Obstetrics and Gynecology

基　　金：中华国际医学会交流基金项目(CIMF-F-H001-313);荆州市科技计划项目(2023HC04);荆州市第一人民医院博士启动项目(2023DIF11)。

摘　　要：目的探讨上皮膜蛋白1(epithelial membrane protein 1,EMP1)在上皮性卵巢癌(epithelial ovarian cancer,EOC)顺铂耐药中的作用及临床意义。方法共收集56例EOC复发再次手术的石蜡标本,采用免疫组化检测EOC组织中EMP1蛋白的表达情况,采用积分光密度(IOD)描述其表达量。采用实时荧光定量PCR(qRTPCR)、蛋白印迹法(Western blot)检测EMP1 mRNA及蛋白在SKOV3及SKOV3/DDP细胞系中的表达情况。采用Cox回归分析评估其对预后影响。结果免疫组化结果显示:顺铂敏感组中EMP1蛋白的IOD值为9.45±3.42,顺铂耐药组为17.70±8.10,差异有统计学意义(P<0.001)。qRT-PCR结果显示,EMP1 mRNA在SKOV3/DDP细胞中的表达显著高于SKOV3细胞(P<0.001)。Western blot结果显示,SKOV3/DDP细胞中EMP1蛋白的表达高于SKOV3细胞(P=0.002)。ROC曲线显示,EMP1表达高、低水平的截断值,IOD的截断值为11.37,ROC曲线下面积为8.821,灵敏度为80.65%,特异度为80.00%。所有患者均已随访到生命终点,EMP1高表达组患者总生存时间(OS)的中位数为14.0个月,而低表达组为23.0个月。Cox回归分析显示,EMP1表达水平与OS显著相关(HR=5.936,P<0.001)。结论EMP1可作为顺铂耐药的标志物,是EOC不良预后的独立危险因素。Objective To investigate the role and clinical significance of epithelial membrane protein 1(EMP1)in cisplatin resistance in epithelial ovarian cancer(EOC).Methods A total of 56 paraffin samples from EOC recurrence reoperation were collected,and the expression of EMP1 protein in EOC tissues was detected by immunohistochemistry,and the expression of protein was described by integrated optical density(IOD).Real-time PCR(qRT-PCR)and Western blot were used to detect the expression of EMP1 mRNA and protein in SKOV3 and SKOV3/DDP cell lines.Cox regression analysis was used to assess its prognostic impact.Results Immunohistochemical results showed that the IOD value of EMP1 protein in cisplatin-sensitive group was 9.45±3.42,and the value was 17.70±8.10 in the cisplatin-resistant group,which was statistically significant(P<0.001).qRT-PCR results showed that the expression of EMP1 mRNA in SKOV3/DDP cells was significantly higher than in SKOV3 cells(P<0.001).Western blot results showed that the expression of EMP1 protein in SKOV3/DDP cells was higher than SKOV3 cells(P=0.002).The ROC curve determined the cut-off values of EMP1 expression at high and low levels,the cut-off value of IOD was 11.37,the area under the ROC curve was 8.821,the sensitivity was 80.65%,and the specificity was 80%.All patients have been followed to the end of life,and the median overall survival time(OS)in the EMP1 high-expression group was 14.0 months(range 8.0~33.0 months),while the low expression group was 23.0 months(range 9.0~55.0 months).Cox regression analysis showed that EMP1 expression level was significantly correlated with OS(HR=5.936,P<0.001).Conclusions EMP1 can be used as a marker of cisplatin resistance and an independent risk factor for the prognosis of EOC.

关 键 词：上皮膜蛋白1 上皮性卵巢癌 顺铂耐药 标志物 

分 类 号：R737.31[医药卫生—肿瘤]