AKT激活与非小细胞肺腺癌吉非替尼耐药性的关系探究

Relationship between AKT Activation and Gefitinib Resistance in Non-small Cell Lung Adenocarcinoma

目的 探讨丝氨酸-苏氨酸蛋白激酶B(AKT)激活与非小细胞肺腺癌吉非替尼耐药性的相关性。方法 选取2020年5月—2022年5月接受吉非替尼治疗的100例非小细胞肺腺癌为研究对象,依据是否发生吉非替尼耐药分为耐药组42例、非耐药组58例。比较2组癌组织中AKT蛋白表达情况。多因素Logistic回归分析吉非替尼耐药性的影响因素。比较耐药组不同临床病理特征患者AKT蛋白表达情况,分析其与临床病理特征相关性。受试者工作特征曲线评价不同影响因素对吉非替尼耐药性的预测效能。结果 耐药组癌组织中AKT蛋白表达水平高于非耐药组(P<0.05)。吸烟史、临床分期、淋巴结转移、AKT蛋白表达水平为非小细胞肺腺癌患者吉非替尼耐药的独立危险因素(P<0.01)。不同临床分期及淋巴结转移患者AKT蛋白表达水平比较差异有统计学意义(P<0.01)。耐药组AKT蛋白表达与临床分期、淋巴结转移呈正相关(P<0.01);AKT蛋白表达预测非小细胞肺腺癌患者吉非替尼耐药的曲线下面积(0.788)分别大于吸烟史(0.697)、临床分期(0.654)、淋巴结转移(0.640)预测(P<0.05,P<0.01)。结论 非小细胞肺腺癌吉非替尼耐药患者中AKT处于活化状态,且与临床分期、淋巴结转移密切相关,其对吉非替尼耐药性具有一定预测价值。

Objective To investigate the correlation between serine-threonine protein kinase B(AKT)activation and Gefitinib resistance in non-small cell lung adenocarcinoma.Methods A total of 100 patients with non-small cell lung adenocarcinoma treated with Gefitinib from May 2020 to May 2022 were selected as the research subjects.According to whether Gefitinib resistance occurred,they were divided into drug resistance group(n=42)and non-drug resistance group(n=58).The expression of AKT protein in two groups of cancer tissues was compared.Multivariate Logistic regression analysis was used to investigate the influencing factors of Gefitinib resistance.The expression of AKT protein in patients with different clinicopathological characteristics in drug resistance group was compared,and its correlation with clinicopathological characteristics was analyzed.The predictive efficacy of different influencing factors on Gefitinib resistance was evaluated by receiver operating characteristic(ROC)curve.Results The expression level of AKT protein in drug resistance group was higher than that in non-drug resistance group(P<0.05).Smoking history,clinical stage,lymph node metastasis and AKT expression level were independent risk factors for Gefitinib resistance in non-small cell lung adenocarcinoma patients(P<0.01).There were significant differences in the expression level of AKT in patients with different clinical stages and lymph node metastasis(P<0.01).In the drug resistance group,AKT expression was positively correlated with clinical stage and lymph node metastasis(P<0.01).The area under the ROC curve(0.788)of AKT expression in predicting Gefitinib resistance in patients with non-small cell lung adenocarcinoma was larger than that of smoking history(0.697),clinical stage(0.654),and lymph node metastasis(0.640),respectively(P<0.05,P<0.01).Conclusion AKT is activated in patients with non-small cell lung adenocarcinoma resistant to Gefitinib,and is closely related to clinical stage and lymph node metastasis,which has a certain predictive value for Gefitinib resistance.