祝彩霞?杨娟?袁林静?牛刚

【摘要】目的 檢测膜突蛋白（MSN）在进展型高级别浆液性卵巢癌（HGSOC）中的表达情况，分析MSN表达上调对卵巢腺癌细胞增殖和侵袭能力的影响。方法 在124例进展型HGSOC标本中应用逆转录PCR检测MSN mRNA的表达情况，分析其与临床特征和预后的关系。体外培养卵巢腺癌细胞OVMZ-6，转染过表达MSN后应用逆转录PCR和蛋白免疫印迹法验证MSN表达变化;分别采用四甲基偶氮唑蓝（MTT）法、Transwell小室实验和流式细胞仪检测MSN表达上调后对卵巢腺癌细胞增殖和侵袭能力的影响。结果 进展型HGSOC标本均能检出MSN mRNA的表达，Kaplan-Meier生存分析显示MSN mRNA高表达者总生存期高于MSN mRNA低表达者（P < 0.05），但无进展生存期组间比较差异无统计学意义（P > 0.05）。多因素Cox回归分析显示MSN mRNA高表达是总生存期的独立保护因素（HR = 0.51，95%CI 0.31 ～ 0.84，P = 0.009）。MSN-pRc/RSV转染后，OVMZ-6细胞中MSN mRNA和蛋白表达水平显著上调。MSN过表达的OVMZ-6细胞增殖能力和侵袭能力明显下降（P均< 0.05）。结论 进展型HGSOC中MSN表达上调可抑制卵巢腺癌细胞的增殖和侵袭能力，影响患者总生存期，提示MSN可能是进展型HGSOC精准治疗的新靶点。

【关键词】高级别浆液性卵巢癌;膜突蛋白;细胞增殖;侵袭;预后

Expression and clinical relevance of moesin in high-grade serous ovarian cancer Zhu Caixia， Yang Juan， Yuan Linjing， Niu Gang. Department of Obstetrics and Gynecology， the First Affiliated Hospital of Sun Yat-sen University， Guangzhou 510080， China

Corresponding author， Niu Gang， E-mail： Niugang@ mail. sysu. edu. cn

【Abstract】Objective To detect the expression level of moesin （MSN） and clinical relevance in advanced high-grade serous ovarian cancer （HGSOC）， and to evaluate the effect of MSN overexpression on cell proliferation and invasiveness in ovarian cancer cell line OVMZ-6. Methods The expression level of MSN mRNA in 124 advanced HGSOC specimens was detected by reverse transcription-polymerase chain reaction （RT-PCR）， and its correlation with clinical characteristics and prognosis was analyzed. After stable transfection with overexpressed MSN， the expression level of MSN mRNA and protein of ovarian cancer cell line OVMZ-6 were determined by RT-PCR and Western blot. The effect of MSN on cell proliferation and invasiveness was evaluated by MTT assay， Transwell chamber assay and flow cytometry in vitro. Results MSN mRNA could be detected in all HGSOC tissues. Kaplan-Meier survival analysis showed that elevated MSN mRNA expression predicted longer overall survival （OS） （P < 0.05）， whereas there was no significant association between MSN mRNA and progression-free survival （PFS） （P > 0.05）. Multivariate Coxs regression analysis demonstrated increased MSN mRNA expression was identified as an independent favorable prognostic factor for OS （HR = 0.51，95%CI 0.31 ～ 0.84，P = 0.009）. The expression levels of MSN mRNA and protein were significantly up-regulated after transfection with MSN-pRc/RSV. The cell proliferation and invasiveness were significantly inhibited in ovarian cancer cells transfected with MSN overexpression （all P < 0.05）. Conclusions Overexpression of MSN can suppress cell proliferation and invasiveness of ovarian cancer cells， resulting in longer OS in patients diagnosed with advanced HGSOC. MSN might serve as a novel therapeutic target in advanced HGSOC.

【Key words】High-grade serous ovarian cancer;Moesin;Cell proliferation;Invasiveness;Prognosis

上皮性卵巢癌是女性生殖道三大恶性肿瘤之一，发病率仅次于宫颈癌，病死率居首位。上皮性卵巢癌主要分为5类：高级别浆液性卵巢癌（HGSOC）、低级别浆液性卵巢癌（LGSOC）、黏液性卵巢癌、透明细胞癌和内膜样癌[1]。HGSOC是主要的上皮性卵巢癌类型，占上皮性卵巢癌死亡病例的70% ～ 80%[2]。由于临床表现不典型和缺乏特异性的检测手段，患者确诊时多为进展型HGSOC（FIGO Ⅲ期或Ⅳ期），治疗方式以手术和化学治疗为主，但自20世纪80年代以来进展型HGSOC的5年总生存期无明显改善，仅为15% ～ 25%[2]。膜突蛋白（MSN）是膜-细胞骨架蛋白（ERM）家族成员之一，主要连接肌动蛋白细胞骨架和细胞膜。……