Keap1、Nrf2蛋白表达与中晚期肺癌化疗敏感性的相关性研究

Correlation between Keap1 and Nrf2 protein expression and chemotherapy sensitivity of advanced lung cancer

目的探讨Kelch样环氧氯丙烷相关蛋白1(Keap1)、核转录因子E2相关因子2(Nrf2)蛋白表达与中晚期肺癌化疗敏感性的关系。方法选取2017年3月~2019年5月哈尔滨医科大学附属第二医院接受一线含铂类方案化疗的首诊中晚期肺癌患者86例,根据世界卫生组织(WHO)实体瘤化疗效果标准分为敏感组54例、不敏感组32例,对比两组肺癌组织标本中Keap1、Nrf2蛋白的表达,并采用logistic回归模型分析Keap1蛋白、Nrf2蛋白的表达与一线含铂类方案化疗敏感性的关系。结果敏感组患者Keap1蛋白的阳性表达率(51.85%)高于不敏感组(28.13%),Nrf2蛋白的阳性表达率(20.37%)低于不敏感组(50.00%),差异均有统计学意义(P<0.05)。TNM分期增加、分化程度降低、发生远处转移、Nrf2蛋白表达增强是中晚期肺癌一线铂类化疗不敏感的独立危险因素(P<0.05);Keap1蛋白表达增强是中晚期肺癌一线铂类化疗敏感的保护因素(P<0.05)。结论中晚期肺癌组织中Keap1蛋白表达增强是一线含铂类方案化疗敏感的保护因素,Nrf2蛋白表达增强是化疗不敏感的危险因素。

Objective To explore the relationship between Keap1,Nrf2 protein expression and chemotherapy sensitivity in advanced lung cancer.Methods 86 patients with advanced lung cancer who received first-line platinum-based chemotherapy in our hospital were divided into 54 cases in the sensitive group and 32 cases in the insensitive group according to the WHO solid tumor chemotherapy standard.Compare Keap1 in lung cancer specimens of the two groups The expressions of protein and Nrf2 protein were analyzed using Logistic regression model to analyze the relationship between the expression of Keap1 protein and Nrf2 protein and the chemotherapy sensitivity of the first-line platinum-containing chemotherapy drugs.Results The positive expression rate of Keap1 protein in the sensitive group was higher than that in the insensitive group(P<0.05),and the positive expression rate of Nrf2 protein in the sensitive group was lower than that in the insensitive group(P<0.05);the logistic regression model was used to model Chemotherapy results were used as dependent variables,with lymph node metastasis,TNM stage,degree of differentiation,distant metastasis rate,Keap1 protein,Nrf2 protein expression as independent variables.The results showed that:TNM stage increased,degree of differentiation decreased,distant metastasis occurred,Nrf2 protein Increased expression is an independent risk factor for insensitivity of first-line platinum chemotherapy in advanced lung cancer(P<0.05),and increased expression of Keap1 protein is a protective factor for the sensitivity of first-line platinum chemotherapy in advanced lung cancer(P<0.05).Conclusion Increased expression of Keap1 protein in advanced lung cancer tissues is a protective factor that is sensitive to chemotherapy for first-line platinum-based chemotherapy drugs,and increased expression of Nrf2 protein is a risk factor for insensitivity to chemotherapy.