自噬相关蛋白在EGFR-TKI耐药NSCLC患者中的表达及其相关性  

Expression and correlation of autophagy-related proteins in EGFR-TKI resistant non-small-cell lung cancer patients

作　　者：张欣伟 王勇 罗辉[1] 刘琴[3] 李勇[1] Zhang Xinwei;Wang Yong;Luo Hui;Liu Qin;Li Yong(Department of Medical Oncology,the First Affiliated Hospital of Nanchang University,Nanchang 330006,China;Department of Medical Oncology,Ganzhou People's Hospital,Ganzhou 341000,China;Department of Respiratory and Critical Care Medicine,the First Affiliated Hospital of Nanchang University,Nanchang 330006,China)

机构地区：[1]南昌大学第一附属医院肿瘤科,江西南昌330006 [2]赣州市人民医院肿瘤科,江西赣州341000 [3]南昌大学第一附属医院呼吸与危重症医学科,江西南昌330006

出　　处：《实用肿瘤杂志》2019年第6期508-512,共5页Journal of Practical Oncology

基　　金：国家自然科学基金(81560379);江西省自然科学基金面上项目(20181BAB205046);江西省科技支撑计划项目(2015BBG70236);江西省教育厅重点项目(GJJ170012)

摘　　要：目的探讨自噬相关蛋白在表皮生长因子酪氨酸激酶受体抑制剂(epidermal growth factor receptor-tyosine kinase inhibitor,EGFR-TKI)耐药非小细胞肺癌(non-small-cell lung cancer,NSCLC)患者中的表达及其相关性。方法选取对吉非替尼敏感(EGFR-S组)和耐药(EGFR-R组)的晚期肺腺癌患者肿瘤组织标本各40例,采用免疫组织化学、Western blot和RT-qPCR检测自噬相关蛋白Beclin1、LC3Ⅱ和p62的表达,并与EGFR耐药进行相关性分析。结果免疫组织化学和Western blot检测显示,与EGFR-S组比较,Beclin1和LC3Ⅱ蛋白在EGFR-R组中表达更低;p62蛋白在EGFR-R组中表达更高(均P<0.05)。RT-qPCR检测显示,EGFR-R组较EGFR-S组Beclin1 mRNA表达下调为(0.55±0.65),LC3ⅡmRNA表达下调为(0.54±0.43),p62 mRNA表达上调为(2.54±0.86)倍(均P<0.05)。Beclin1和LC3Ⅱ蛋白(r=-0.723,r=-0.705)及mRNA(r=-0.462,r=-0.417)表达与EGFR耐药负相关(均P<0.01),p62蛋白(r=0.742,P<0.01)及mRNA(r=0.460,P<0.01)表达与EGFR耐药正相关。结论自噬水平的低下与EGFR-TKI耐药密切相关,自噬表达水平与EGFR-TKI耐药的出现呈负性相关。Objective To explore the expression and correlation of autophagy-related proteins in epidermal growth factor receptor-tyosine kinase inhibitor(EGFR-TKI)resistant non-small-cell lung cancer(NSCLC)patients.Methods Eighty lung adenocarcinoma tissues which were sensitive or resistant to gefitinib were collected.The patients were divided into the EGFR-TKI sensitive(EGFR-S)group and EGFR-TKI resistant(EGFR-R)group.The expression of autophagy-related proteins Beclin1,LC3Ⅱand p62 were detected by immunohistochemisty,Western blot and RT-qPCR.In addition,a correlation analysis was made between autophagy-related proteins and EGFR-TKI resistance.Results Immunohistochemistry and Western blot analysis showed that the expressions of Beclin1 and LC3Ⅱproteins were lower and the expression of p62 protein was higher in the EGFR-R group than those in the EGFR-S group(all P<0.05).RT-qPCR showed that the mRNA expression of Beclin1 in the EGFR-R group was down-regulated to(0.55±0.65)compared with that in the EGFR-S group,the mRNA expression of LC3Ⅱwas down-regulated to(0.54±0.43),but the mRNA expression of p62 was up-regulated to(2.54±0.86)(all P<0.05).The expressions of proteins and mRNA of Beclin1(r=-0.723,r=-0.462)and LC3Ⅱ(r=-0.705,r=-0.417)were positively correlated with EGFR-TKI resistance,but the expression of protein and mRNA of p62(r=0.742,r=0.460)was negatively correlated with EGFR-TKI resistance(all P<0.01).Conclusions The low expression of autophagy is closely related to EGFR-TKI resistance,and there is significant negative correlation between the expression levels of autophogy related proteins and EGFR-TKI resistance.

关 键 词：癌 非小细胞肺/药物疗法 肺肿瘤/药物疗法 自除 蛋白酪氨酸激酶类/治疗应用 蛋白酪氨酸激酶类/拮抗剂和抑制剂 受体 表皮生长因子/治疗应用 抗药性 肿瘤 免疫组织化学 

分 类 号：R734.2[医药卫生—肿瘤] R730.53[医药卫生—临床医学]