p53及耐药相关基因的表达与非小细胞肺癌化疗耐药性的研究

目的探讨p53突变与耐药相关基因表达的相关性及其与肺癌化疗耐药的关系。方法免疫组化检测60例非小细胞肺癌组织的p53和耐药相关蛋白P-gp、MRP、LRP、GST-π的表达并分析其相关性及其与肺癌化疗耐药的关系。结果 P-gp、MRP、LRP、GST-π、p53阳性率分别为53.3%、50.0%、75.0%、73.3%、68.3%。LRP在腺癌中表达最高,p53在鳞癌中表达最高。p53的表达与肿瘤细胞分化程度、有无淋巴结转移和TNM分期密切相关,其余4种耐药相关蛋白表达差异均无统计学意义（P〉0.05）。p53和一种或一种以上耐药相关蛋白共表达率达94.8%,且p53与P-gp、GST-π的表达存在正相关性（P均〈0.05）。p53蛋白的表达与化疗疗效显著相关,p53阴性化疗有效率（60.5%）明显高于p53阳性者（28.3%,P〈0.05）。结论肺癌组织p53突变与耐药相关蛋白的表达有相关性,p53结合耐药相关蛋白检测可以预示患者的化疗耐药性,对个体化化疗方案的制定具有指导意义。

Study on the correlation between expression of p53/MDR and drug resistance in non-small cell lung cancer

Objective To investigate the relationship between p53 mutation and the expression of multi-drug resistance（MDR）genes.Methods Immunohistochemical staining was employed to detect 60 lung cancer tissues for p53 and MDR.Results The positive rates of p53 and P-gp,MRP,LRP,GST-π in NSCLC were 68.3%,53.3%,50.0 %,75.0% and 73.3%,respectively,and the highest expression in adenocarcinoma was LRP and in squamous cell carcinoma was p53.The expression of p53 was significantly related with differential degree and TNM and lymph node metastasis.The co-expression rate of p53 and one or more MDR was 94.8%.Significant correlations were found between p53 and expression of either P-gp or GST-π（P〈0.05）.p53-negative chemotherapy efficiency（60.5%）was significantly higher than p53-positive（28.3%,P〈0.05）.Conclusion p53 mutation in NSCLC was closely correlated with the expression of MDR,assays of p53 and these MDR proteins will be useful to personalize chemotherapy of lung cancer clinically.