肺腺癌EGFR基因突变与多重耐药相关蛋白表达的临床意义

Clinical significance of EGFR gene mutation and the expression of proteins associated with multi-drug resistance in lung adenocarcinoma

目的探讨肺腺癌EGFR基因突变、多重耐药相关蛋白(MDR1、TopoⅡ、MVP、GST pi)表达与临床病理特征的关系。方法回顾性筛选烟台市烟台山医院2017年5月至2021年12月外科手术切除或穿刺活检之肺原发性浸润性腺癌标本,采用等位基因特异扩增荧光聚合酶链反应和免疫组织化学法检测肺腺癌EGFR基因突变和多重耐药相关蛋白表达。分析临床病理特征与EGFR基因突变状态、多重耐药相关蛋白表达的关系。结果共筛选出EGFR基因突变标本273例。肺腺癌患者性别、吸烟史、肿瘤大小、分化程度、淋巴结转移、TNM分期与EGFR基因突变状态密切相关(均P<0.05)。肺腺癌患者年龄、肿瘤大小、淋巴结转移、TNM分期与MDR1蛋白表达程度密切相关(均P<0.05);吸烟、肿瘤大小、分化程度、淋巴结转移、TNM分期与TopoⅡ蛋白表达程度密切相关(均P<0.05)。MDR1和GST pi蛋白在EGFR不同突变类型肺腺癌中的表达程度不同(均P<0.05),且肺腺癌间质中MDR1蛋白表达程度与EGFR基因突变类型密切相关(P<0.05)。结论肺腺癌组织存在一定的内源性多重耐药,肿瘤间质微环境可能在肺腺癌的多重耐药中起作用。

Objective To investigate the correlation between mutation of EGFR gene,the expression of proteins(MDR1,TopoⅡ,MVP,GST pi)associated with multi-drug resistance and clinicopathological features in lung adenocarcinoma.Methods Primary invasive lung adenocarcinoma specimens surgically resected or biopsied from Yantai Mountain Hospital from May 2017 to December 2021 were retrospectively selected.The allele-specific amplification fluorescent polymerase chain reaction and the immunohistochemical method were carried out to detect EGFR mutation and the expression of proteins associated with multi-drug resistance in lung adenocarcinoma.The relationship between the clinicopathological features and the EGFR gene mutation status,the expression of proteins associated with multi-drug resistance in lung adenocarcinoma were analyzed.Results A total of 273 samples with EGFR gene mutations were selected.The mutation types of EGFR gene was significantly associated with sex,smoking,tumor size,differentiation degree,lymph node metastasis and clinical TNM staging,respectively(all P<0.05).The expression degree of MDR1 protein was significantly correlated with age,tumor size,lymph node metastasis and clinical TNM staging,respectively(all P<0.05).The expression degree of TopoⅡprotein was significantly correlated with smoking,tumor size,differentiation degree,lymph node metastasis and clinical TNM stage,respectively(all P<0.05).The expression degree of MDR1 and GST pi protein in lung adenocarcinoma with different mutation types of EGFR was significantly different(all P<0.05).In addition,there was a significant difference between EGFR gene mutations and MDR1 protein expression degree of stromal elements in lung adenocarcinoma(P<0.05).Conclusion Endogenous multi-drug resistance exists in lung adenocarcinoma tissues,and the tumor mesenchymal microenvironment may play a role in the multi-drug resistance of lung adenocarcinoma patients with different EGFR mutations.