IGF信号通路与肺腺癌EGFR-TKI治疗获得性耐药的关系

Relationship between Insulin-Like Growth Factor Signaling Pathway and Drug Resistance of EGFR-TKI Therapy in Lung Adenocarcinoma

目的探究胰岛素样生长因子信号通路在肺腺癌EGFR-TKI治疗获得性耐药中的作用。方法采用免疫组织化学SP法检测64例肺腺癌组织和16例正常肺组织中IGF1R和EGFR的表达,ELISA法检测晚期肺腺癌患者血清中IGF1的含量。结果 IGF1R在肺腺癌组织中的表达与对照组无显著差异,IGF1R的表达与患者各临床病理参数无显著相关性(P>0.05)。EGFR在肺腺癌组织中的表达显著高于对照组,且EGFR的表达受肿瘤分化程度、浸润深度、淋巴结转移及分期的影响(P<0.05)。IGF1R与EGFR在肺腺癌患者中的表达显著相关(P<0.05);在晚期接受EGFR-TKI治疗的肺腺癌患者中,病情进展后血清中IGF1的含量较治疗前显著增高(P<0.05)。结论胰岛素样生长因子信号通路在肺腺癌患者EGFR-TKI治疗获得性耐药中起一定作用。

Objective To explore the relationship between insulin-like growth factor（ IGF） signaling pathway drug resistance of EGFR-TKI therapy in lung adenocarcinoma. Methods The expression of IGF1 R and EGFR were detected by streptavidin perotridase in 64 cases of lung adenocarcinoma tissues and 16 cases of normal lung tissues. The content of IGF1 in serum of patients with advanced lung adenocarcinoma were detected by ELISA. Results There were no significant differences in IGF1 R expression between the 2 groups and the expression of IGF1 R also had no significant correlation with clinicopathologic parameters（ P〉0. 05）. The expression of EGFR in the lung adenocarcinoma was significantly higher than that of the control group and was associated with degrees of differentiation,depth of invasion,lymph nodes metastasis and stages（ P〈0. 05）. The expression of IGF1 R in patients with lung adenocarcinoma was significantly associated with EGFR（ P〈0. 05）. The serum level of IGF1 in patients with advanced lung adenocarcinoma significantly increased after resistance to EGFR-TKI therapy（ P〈0. 05）. Conclusion IGF signaling pathway plays a certain role in acquired resistance to EGFR-targeted therapy in lung adenocarcinoma.