MTOR Signaling Pathway And Lung Surgery

Background:Non-small cell lung cancer (NSCLC) remains a highly lethal disease worldwide. The EGFR/PI3K/Akt/mTOR signal pathway is closely related with the development and progress of NSCLC. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) have been widely used for the treatment of anvanced NSCLC, and the EGFR mutation is recognized as the most important predictor of the response to EGFR-TKI. EGFR-TKI used for postoperative patients is rarely reported, and sequentially, the efficacy of the treatment and the predictors are unkown there.Purpose:Investgate the basic situation of the expression of p-mTOR、p-4EBP1、 EIF4E and EGFR mutation, and evaluate the correlation with the clinical characteristics, the response of EGFR-TKI and the prognosis. The activity of EGFR-TKI used for postoperative patients were evaluated too.Methods:356patients who were diagnosed as lung adenocarcinoma and operated on from2001through2011were studied, and257patients out of them were successfully followed up. Expression of p-mTOR、p-4EBP1、EIF4E was detected by Western Blot in99of them. Data evaluation was carried out with SPSS13.0statistical software.Results:EGFR mutation was detected in161patients, and59.0%of them showed positive results. People who didn’t smoke or diagnosed as well differentiated tumor, would have more chance of EGFR mutation. The expression of p-mTOR、EIF4E in tumor specimen was significantly higher than that of adjacent tissues. Correlation of the expression of p-mTOR、p-4EBP1、EIF4E was observed. However, between the expression of those three proteins and EGFR mutation, there wasn’t such correlation. Postoperative recurrent lung adenocarcinoma patients may get longer median OS if treated with EGFR-TKI (significantly in phase Ⅲ). But this study didn’t get a conclusion about whether patients who didn’t have any progress after the operation should be treated with EGFR-TKI. Evaluation of the activity and efficacy of EGFR-TKI in patients after operation is more difficult than in anvanced NSCLC patients, because the point for evaluation is less (only PFS and OS), and longer time for following up is needed, and the time to start with the EGFR-TKI treatment is heterogeneous. Therefore, Prospective Studies and longer-time follow up studies should be executed to evaluate EGFR-TKI using in operative patients.Conclusion:The positive rate of EGFR mutation in adenocarcinoma is59.0%, and people who didn’t smoke, or dignosed as diabronchioloalveolar cell carcinoma, or with well differentiated tumor, would have more chance of EGFR mutation positive. The expression of p-mTOR、EIF4E in tumor specimen was significantly higher than that of adjacent tissues, and the expression of p-mTOR、p-4EBP1and EIF4E correlated with eachother, but not with the EGFR mutation. Prospective Studies and longer-time follow up studies should be executed to evaluate EGFR-TKI using in operative patients.