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多药耐药基因1(MDR1)在上皮性卵巢癌中的表达及其与疾病进展的关系。

Expression of MDR1 in epithelial ovarian cancer and its association with disease progression.

作者信息

Lu Lingeng, Katsaros Dionyssios, Wiley Andrew, Rigault de la Longrais Irene A, Puopolo Manuela, Yu Herbert

机构信息

Department of Epidemiology and Public Health, Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520-8034, USA.

出版信息

Oncol Res. 2007;16(8):395-403. doi: 10.3727/000000006783980892.

Abstract

The purposes of this study were to analyze MDR1 expression in ovarian tumors prior to chemotherapy, to correlate the expression with p16, IGFs, ERalpha, and BRCA1, and to examine the association of MDR1 expression with ovarian cancer prognosis. A primary ovarian cancer cohort of 206 patients after surgery was followed up. MDR1, IGFs, ERalpha, p16, and BRCA1 expressions were analyzed in ovarian tumor samples using quantitative real-time PCR. MDR1 was detected in 177 of 206 specimens. MDR1 expression was positively correlated with IGFBP3, ERalpha, p16, and BRCA1, but not correlated with IGF-II, age, and other clinicopathological parameters. MDR1 expression significantly elevated the risk for disease progression (p = 0.02), and this association remained statistically significant after controlling for patient age and clinicopathological parameters or other correlated genes. No association was found between MDR1 expression and overall survival. MDR1 expression may be an independent marker for ovarian cancer progression and combination of different agents targeting different molecules may improve the outcome of ovarian cancer treatment and prevent drug resistance.

摘要

本研究的目的是分析化疗前卵巢肿瘤中MDR1的表达,将该表达与p16、胰岛素样生长因子(IGFs)、雌激素受体α(ERalpha)和乳腺癌1号基因(BRCA1)进行关联分析,并研究MDR1表达与卵巢癌预后的关系。对206例手术后的原发性卵巢癌患者队列进行随访。使用定量实时聚合酶链反应(PCR)分析卵巢肿瘤样本中MDR1、IGFs、ERalpha、p16和BRCA1的表达。在206个标本中的177个检测到MDR1。MDR1表达与胰岛素样生长因子结合蛋白3(IGFBP3)、ERalpha、p16和BRCA1呈正相关,但与胰岛素样生长因子-II(IGF-II)、年龄和其他临床病理参数无关。MDR1表达显著增加疾病进展风险(p = 0.02),在控制患者年龄、临床病理参数或其他相关基因后,这种关联仍具有统计学意义。未发现MDR1表达与总生存期之间存在关联。MDR1表达可能是卵巢癌进展的独立标志物,联合使用针对不同分子的不同药物可能改善卵巢癌治疗效果并预防耐药性。

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