The Relationship Between Epithelial-mesenchymal Transition, The Expression Of IGF-1R And Efficacy Of Gefitinib As The Second Line Treatment For Advanced Non-small Cell Lung Cancer

Objective: To explore the relationship between the epithelial-mesenchymal transition(EMT),the expression of insulin-like growth factor-1 recptor(IGF-1R) and the efficacy of gefitinib as the second line treatment for advanced non-small cell lung cancer(NSCLC).Methods:Clinic and pathologic data of 76 patients withⅣstage NSCLC who were treated with gefitinib as the second line treatment were collected.The expression of E-cadherin,Vimentin and IGF-1R was determined by immunohistochemical staining.The E-cadherin(-) and Vimentin (+) was defined as EMT(+),E-cadherin (+)and Vimentin(-) was defined as EMT(-). The gene mutation of epidemal growth factor receptor(EGFR) was dected in 43 samples by liquid chips assay.The efficacy gefitinib was evaluated by CT scan,and the objective response rate(ORR),disease response rate(DCR) and overall survival(OS)were calculated.The relationship between the expression of EMT,IGF-1R and clinicpathologic features,the expression of EMT and IGF-1R,and the expression of EMT,IGF-1R and the gene mutation of EGFR were analysized in order to explore the effect of the expression of EMT and IGF-1R on the efficacy of gefitinib and overall survival.Results:The positive rate of IGF-1R,E-cadherin and Vimentin in 76 patients was 64.5%,46.1% and 53.9%,respectively. The EMT was not correlated with clinicopathological characteristics.However,the IGF-1R expression was related to histological types.The positive rate of IGF-1R was significantly higher in the non-adrenocarcinoma patients than that in adrenocarcinoma patients[22/28(78.5%) VS 27/48(56.2%)].A slight but statistical significant correlation was found between EMT and IGF-1R(r=0.252,P=0.028).The EMT(-) was more frequently observed in the patients with EGFR mutation.However,the expression of IGF-1R was not associated with EGFR mutation status.Both DCR and ORR in EMT(-) patients were significantly higher than that in EMT(+) patients(DCR:65.7% versus 24.3%.p<0.05;ORR:37.1% versus 9.8%,p<0.05),and also were significantly higher in IGF-1R(-) patients than that in IGF-1R(+) patients(DCR:66.7% versus 30.6%,p<0.05;ORR:37.0% versus 14.3%,p<0.05).The EMT(-) patients had a signif icantly longer median overall survival (10.0 months vs. 5.0 months,p<0.05) . The median overall survival was 8.0 months in the IGF-1R(-) patients and 5.0 months in the IGF-1R(+) patients(p>0.05) In the patients with EGFR mutations,the EMT(-) patients showed relative hogher ORR than EMT(+) patients.In the patients with wild-type EGFR,the highest ORR was found in those with both EMT(-) and IGF-1R(-)Conclusion: EMT and the expression of IGF-1R might be associated with the efficacy of gefitinib,and may be one of the predictive factors for efficacy of gefitinib as the second line therapy for advanced NSCLC.