高级别卵巢浆液性癌组织中ETAR mRNA表达的临床意义及ETAR来源融合多肽抑癌作用的研究  

Study of the clinical significance of ETAR mRNA expression in high-grade serous ovarian cancer and the inhibitory effect of ETAR derived fusion polypeptide on cancer progression

作　　者：张艳玲[1] 夏晓琨 张梦[1] Zhang Yanling;Xia Xiaokun;Zhang Meng(Department of Obstetrics and Gynecology,Central Hospital of Xuzhou,Xuzhou 221009,China)

机构地区：[1]徐州市中心医院妇产科,徐州221009

出　　处：《中华妇产科杂志》2023年第12期930-938,共9页Chinese Journal of Obstetrics and Gynecology

摘　　要：目的探讨高级别卵巢浆液性癌(HGSOC)组织中内皮素A受体(ETAR)表达的临床意义;设计ETAR羧基末端(ETAR-C)氨基酸序列来源的ETAR-C融合多肽,研究其对卵巢上皮性癌(卵巢癌)细胞的体外抑癌作用。方法(1)选择2007年1月1日至2017年12月31日在徐州市中心医院接受手术治疗、术后病理检查确诊为HGSOC且有完整临床病理资料及随访资料的患者共126例,收集其癌组织标本,采用逆转录-PCR技术检测HGSOC组织中ETAR mRNA的表达,并分析其临床意义。(2)以ETAR-C氨基酸序列为基础设计ETAR-C融合多肽,通过体外表达、纯化ETAR-C融合多肽,采用划痕实验、侵袭实验分别检测ETAR-C融合多肽处理后卵巢癌SKOV3和CAOV3细胞的迁移、侵袭能力,四甲基偶氮唑蓝(MTT)比色法检测ETAR-C融合多肽处理后顺铂耐药卵巢癌SKOV3/cDDP和CAOV3/cDDP细胞的化疗敏感性,蛋白印迹(western blot)法检测ETAR-C融合多肽处理后卵巢癌SKOV3和CAOV3细胞中β抑制蛋白1(β-arrestin-1)的表达。结果(1)HGSOC组织中ETAR mRNA的相对表达水平为18.6±5.1,X-Tile软件分析显示最佳截断值为61.7%,据此将HGSOC患者分为ETAR mRNA高表达(76例)和低表达(50例)。ETAR mRNA高表达与HGSOC患者的腹水量、铂类药物耐药和血清癌抗原125(CA125)水平均显著有关(P均<0.05),而与HGSOC患者的年龄、术后残留灶大小无关(P均>0.05);ETAR mRNA高表达和低表达患者的5年无进展生存率分别为18.4%、28.0%,5年总生存率分别为38.2%、52.0%,两者分别比较,差异均有统计学意义(P=0.046,P=0.034)。(2)划痕实验和侵袭实验结果均显示,内皮素1(ET-1)、ET-1+ETAR-C分别处理后SKOV3和CAOV3细胞的划痕愈合率和细胞侵袭率分别比较,差异均有统计学意义(P均<0.05)。MTT比色法检测显示,加入不同浓度(4、6、8、10、12、24μg/ml)顺铂后,ETAR-C融合多肽处理后的SKOV3/cDDP和CAOV3/cDDP细胞的抑制率均显著高于对照细胞(P均<0.05)。western blot法检测显示Objective To investigate the clinical significance of endothelin A receptor(ETAR)expression in high-grade serous ovarian carcinoma(HGSOC).To design ETAR carboxyl terminal(ETAR-C)amino acids derived polypeptide and to study the inhibitory effect on ovarian epithelial carcinoma cells in vitro.Methods(1)A total of 126 patients who received surgical treatment and were diagnosed with HGSOC by postoperative pathological examination in Central Hospital of Xuzhou from January 1,2007 to December 31,2017 were selected.All patients had completed clinicopathological data and follow-up data.Cancer tissue samples were collected and ETAR mRNA expression in HGSOC tissues was detected by reverse transcript-PCR.The clinical significance was analyzed.(2)ETAR-C fusion polypeptide was designed based on the sequence of carboxyl terminal amino acids of ETAR,expressed and purified in vitro.The effects of ETAR-C fusion polypeptide on migration and invasion ability of ovarian cancer SKOV3 and CAOV3 cells were detected by scratch test and invasion test,respectively.The effect of ETAR-C fusion polypeptide on chemosensitivity of cisplatin-resistant ovarian cancer SKOV3/cDDP and CAOV3/cDDP cells was determined by methyl thiazolyl tetrazolium(MTT)colorimetric assay.The effect of ETAR-C fusion polypeptide onβ-arrestin-1 expression in ovarian cancer SKOV3 and CAOV3 cells was detected by western blot.Results(1)The relative expression level of ETAR mRNA in HGSOC tissues was 18.6±5.1.Patients with HGSOC were divided into high ETAR mRNA expression(n=76)and low ETAR mRNA expression(n=50)with 61.7%as cut-off value analyzed by X-Tile software.High expression of ETAR mRNA was significantly correlated with abdominal water volume,platinum drug resistance,and cancer antigen 125(CA125)value in HGSOC patients(all P<0.05),but was not related to the age of patients with HGSOC and the size of postoperative residual lesions(all P>0.05).The 5-year progression free survival rates were 18.4%and 28.0%,and the 5-year overall survival rates were 38.2% and 52.0% in H

关 键 词：卵巢肿瘤 囊腺癌 浆液 受体 内皮素A 肽类 细胞运动 肿瘤浸润 

分 类 号：R737.31[医药卫生—肿瘤]