四硝酸戊赤藓醇和小鼠核因子κB亚基p65亲和肽在上皮性卵巢癌中的表达及与顺铂耐药性的研究

Study on the expressions of pentaerythritol tetranitrate and mouse nuclear factor-κB subunit p65 affinity peptide in epithelial ovarian cancer and durg resistance of cisplatin

目的探讨四硝酸戊赤藓醇(PTEN)和小鼠核因子κB亚基p65亲和肽(NFκB p65)在上皮性卵巢癌中的表达以及与患者顺铂耐药性及预后的关系。方法选取2009年1月-2015年12月在河北医科大学第四医院妇产科治疗的161例上皮性卵巢癌患者,并根据患者对顺铂化疗的敏感性分为敏感组82例和耐药组79例。免疫组化检测患者肿瘤组织中PTEN和NFκB p65蛋白的表达,分析PTEN和NFκB p65蛋白表达与上皮性卵巢癌患者顺铂耐药的关系。Cox回归模型分析上皮性卵巢癌患者预后的独立危险因素。结果 68.29%的敏感组患者肿瘤组织中表达NFκB p65蛋白,明显低于耐药组患者(94.94%);50.0%的敏感组患者肿瘤组织中表达PTEN蛋白,明显高于耐药组患者(17.72%)。上皮性卵巢癌患者卵巢组织中NFκB p65蛋白表达与PTEN蛋白呈显著负相关(r_s=-0.246,P=0.002)。NFκB p65和PTEN蛋白以及手术分期是卵巢癌患者发生耐药的独立危险因素(P<0.05)。结论 PTEN蛋白低表达或NFκB p65蛋白高表达是上皮性卵巢癌患者发生耐药性的独立危险因素。

Objective To explore the expressions of pentaerythritol tetranitrate（ PTEN） and mouse nuclear factor-κB subunit p65（ NFκB p65） affinity peptide in epithelial ovarian cancer and the relationships with durg resistance of cisplatin and prognosis. Methods A total of 161 epithelial ovarian cancer patients treated in the Fourth Hospital of Hebei Medical University from January 2009 to December 2015 were selected and divided into drug sensitivity group（ 82 patients） and drug resistance group（ 79 patients） according to the sensitivity to cisplatin. Immunohistochemical method was used to detect the expressions of PTEN protein and NFκB p65 protein. The relationships between expressions of PTEN protein and NFκB p65 protein and drug resistance of cisplatin in epithelial ovarian cancer patients were analyzed. Cox model was used to analyze the independent risk factors of prognosis of epithelial ovarian cancer patients. Results In drug sensitivity group,NF-κB p65 protein expressed in 68. 29% of the patients,which was significantly lower than that in drug resistance group（ 94. 94%）. In drug sensitivity group,PTEN protein expressed in 50. 0% of the patients,which was significantly higher than that in drug resistance group（ 17. 72%）. The expression of NF-κB p65 protein was significantly correlated with expression of PTEN protein in ovarian tissue of epithelial ovarian cancer patients（ rs=-0. 246,P = 0. 002）. NFκB p65 protein,PTEN protein,and surgical staging were independent risk factors of drug resistance in epithelial ovarian cancer patients（ P 0. 05）. Conclusion Down-regulation of PTEN protein and up-regulation of NF-κB protein are independent risk factors of drug resistance in epithelial ovarian cancer patients.