Napsin A与上皮-间充质转化标志物在晚期肺腺癌EGFR-TKIs获得性耐药前后的表达及其相关性  

Expression and correlation of Napsin A and epithelial-mesenchymal transition markers before and after acquired drug resistance to EGFR-TKIs in advanced lung adenocarcinoma

作　　者：徐军[1] 姬园园 程兰兰 王健[1] 吕东来 XU Jun;JI Yuanyuan;CHENG Lanlan;WANG Jian;LU Donglai(Department of Pathology,the 901st Hospital of the Joint Logistics Support Force of PLA,Hefei 230031;Division 1,Department of Oncology,the 901st Hospital of the Joint Logistics Support Force of PLA,Hefei 230031,China)

机构地区：[1]中国人民解放军联勤保障部队第九○一医院病理科,合肥230031 [2]中国人民解放军联勤保障部队第九○一医院肿瘤一科,合肥230031

出　　处：《临床与病理杂志》2023年第8期1477-1485,共9页Journal of Clinical and Pathological Research

基　　金：联勤保障部队第九〇一医院院管重点课题(2021YGZD02)。

摘　　要：目的近年来体外细胞实验证实,肺癌细胞发生上皮-间充质转化(epithelial-mesenchymal transition,EMT)与表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitors,EGFR-TKIs)耐药密切相关,而Napsin A表达上调可逆转吉非替尼耐药的肺癌细胞中的EMT,恢复细胞对吉非替尼的敏感性。但Napsin A及EMT标志物与晚期肺腺癌患者EGFR-TKIs耐药之间的关系知之甚少。本研究旨在探讨晚期肺腺癌EGFR-TKIs获得性耐药前后Napsin A的表达变化及其与EMT标志物的相关性。方法收集一线接受EGFR-TKIs治疗且治疗前和获得性耐药后均有活体组织检查的晚期肺腺癌患者52例,采用免疫组织化学EnVision两步法检测Napsin A、上皮钙黏素(E-cadherin)和波形蛋白(Vimentin)的表达。结果Napsin A、E-cadherin和Vimentin在EGFR-TKIs治疗前、耐药后均可见异常表达,耐药后Napsin A和Vimentin异常表达率均高于治疗前(均P<0.05),异常表达均与国际肺癌研究协会分级呈正相关(P<0.01),而与敏感突变类型、继发性T790M突变均无显著相关性。Spearman相关分析显示:E-cadherin表达与Vimentin表达呈负相关(r=-0.300,P=0.002);Napsin A表达与E-cadherin表达呈正相关(r=0.328,P=0.001),与Vimentin表达呈负相关(r=-0.433,P<0.001)。Napsin A、E-cadherin正常表达组客观缓解率均高于原发或获得性异常表达组(均P<0.05)。Kaplan-Meier生存分析显示:Napsin A、E-cadherin和Vimentin原发或获得性异常表达患者的无进展生存期较正常表达患者更短。结论Napsin A、E-cadherin和Vimentin可以作为预测EGFR突变的晚期肺腺癌EGFR-TKIs疗效的参考指标,Napsin A可能通过参与EMT过程影响EGFR-TKIs的敏感性。Objective Recently,in vitro cell experiments have confirmed that epithelial-mesenchymal transition(EMT)in lung cancer cells is closely associated with epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)resistance,and the upregulation of Napsin A expression can reverse EMT in gefitinib-resistant lung cancer cells and restore the sensitivity of cells to gefitinib.However,the relationship of Napsin A and EMT markers with EGFR-TKIs resistance in advanced lung adenocarcinoma patients and prognosis remains poorly understood.This study aims to investigate the changes of Napsin A expression before and after acquired resistance of EGFR-TKIs in advanced lung adenocarcinoma and its correlation with EMT markers.Methods A total of 52 paired specimens from patients with advanced lung adenocarcinoma treated with first-line EGFR-TKIs before treatment and after acquired resistance were collected,and the expression of Napsin A,E-cadherin,and Vimentin was detected by immunohistochemical EnVision two-step method.Results Abnormal expression of Napsin A,E-cadherin,and Vimentin proteins was observed before and after the treatment with EGFR-TKIs,and the abnormal expression rates after resistance were both higher than those before the treatment(both P<0.05).The abnormal expression of all 3 proteins was positively correlated with the International Association for the Study of Lung Cancer grade(P<0.01),but showed no significant correlation with EGFR mutation type or secondary T790M mutation.Spearman correlation analysis showed that E-cadherin expression was negative associated with Vimentin expression(r=-0.300,P=0.002),Napsin A expression was significantly positive associated with E-cadherin expression(r=0.328,P=0.001),but was negative associated with Vimentin expression(r=-0.433,P<0.001).The objective response rates in the Napsin A and E-cadherin normal expression groups were both higher than those in the primary or acquired Napsin A and E-cadherin abnormal expression groups(both P<0.05).Kaplan-Meier survival analysis s

关 键 词：肺腺癌 表皮生长因子受体 酪氨酸激酶抑制剂 Napsin A 上皮-间充质转化 获得性耐药 

分 类 号：R734.2[医药卫生—肿瘤]