EGFR突变和CIP2A表达与肺腺癌临床特征的关系及相关性  

Relationship between CIP2A expression,EGFR mutation and clinical characteristics of patients with lung adenocarcinoma

作　　者：孙晓静[1] 陈颖[2] 阮婷[2] 吕彦天[2] SUN Xiao-jing;CHEN Ying;RUAN Ting;LV Yan-tian(Department of Pathology,the First Affiliated Hospital of Soochow University,Suzhou 215006,China;Department of Respiratory and Critical Medicine,Affiliated Suzhou Hospital of Nanjing Medical University,Suzhou 215002,China)

机构地区：[1]苏州大学附属第一医院病理科,苏州215006 [2]南京医科大学附属苏州医院呼吸与危重医学科,苏州215002

出　　处：《临床与实验病理学杂志》2022年第12期1445-1451,共7页Chinese Journal of Clinical and Experimental Pathology

基　　金：苏州市科教兴卫青年科技项目(KJXW2018027)。

摘　　要：目的探讨CIP2A表达和EGFR突变状态与肺腺癌患者临床特征的关系及相关性。方法收集105例肺腺癌及78例癌旁组织的临床资料,ARMS法检测EGFR突变,免疫组化及Western blot法检测CIP2A表达水平,分析两者与临床特征的关系;以EGFR耐药突变肺癌细胞株H1975构建干扰CIP2A肺癌细胞模型,探讨干扰CIP2A后肺癌细胞株的生物学行为。结果肺腺癌组织中CIP2A表达(64.76%)明显高于癌旁组织(8.97%,P<0.001),EGFR突变与CIP2A表达呈正相关(r=0.650,P<0.001)。Kaplan-Meier生存分析显示:病理分期(P=0.002)、CIP2A表达(P=0.015)、EGFR突变状态(P=0.003)是影响患者预后的相关因素。CIP2A在EGFR突变及继发耐药细胞株中的表达较高。H1975 CIP2A干扰细胞株较空载体肺癌细胞株的增殖、周期、迁移及侵袭能力均受抑制(P<0.01)。加入吉非替尼后,H1975 CIP2A干扰细胞株增殖明显弱于空载体肺癌细胞株(OD值1.72±0.18 vs 2.84±0.25,P<0.01),表明干扰CIP2A可一定程度上恢复EGFR耐药突变肺癌细胞对EGFR-TKI的敏感性。结论CIP2A与EGFR突变呈正相关,EGFR-TKI耐药可能与CIP2A高表达有关,干扰CIP2A可成为肺癌治疗的新思路。Purpose To explore the relationship between CIP2A expression,EGFR mutation and clinical characteristics of patients with lung adenocarcinoma and its mechanism.Methods The clinicopathological data were collected in 105 cases of 0-Ⅳlung adenocarcinoma and 78 cases of paracancerous tissues.The mutation of EGFR was detected by ARMS method,the expression level of CIP2A was detected by immunohistochemical and Western blot analysis,and the relationship between them and clinical features was analyzed.The lung cancer cell model interfering with CIP2A was established by EGFR drug resistant mutant H1975 cell line,and the biological behavior of lung cancer cell line after interfering with CIP2A was studied.Results The expression of CIP2A in lung adenocarcinoma(64.76%)was significantly higher than that in adjacent tissues(8.97%,P<0.001),and there was a positive correlation between EGFR mutation and CIP2A expression(r=0.650,P<0.001).Kaplan-Meier survival analysis showed that pathological stage(P=0.002),CIP2A expression level(P=0.015)and EGFR mutation status(P=0.003)were the relevant factors affecting prognosis.CIP2A was highly expressed in EGFR mutant and secondary drug resistant cell lines.The proliferation,cycle,migration and invasion of H1975 CIP2A interference cell line were significantly lower than those of empty vector lung cancer cell line(P<0.01).After the addition of gefitinib,the proliferation of H1975 CIP2A interference cell line was significantly weaker than that of empty vector lung cancer cell line(OD value 1.72±0.18 vs 2.84±0.25,P<0.0 l),indicating that interference CIP2A could restore the sensitivity of EGFR resistant mutant lung cancer cells to epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)to some extent.Conclusion There is a positive correlation between CIP2A and EGFR mutation.The drug resistance of EGFR-TKI may be related to the high expression of CIP2A,and interfering with CIP2A may become a new idea for targeted therapy of lung cancer.

关 键 词：肺肿瘤 腺癌 EGFR突变 耐药 CIP2A 临床特征 

分 类 号：R734.2[医药卫生—肿瘤]