Epithelial Mesenchymal Transition and its Roles on Chemoresistance in Non―small Cell Lung Cancer.doc

Epithelial Mesenchymal Transition and its Roles on Chemoresistance in Non―small Cell Lung Cancer Abstract Objective：Previous reported have demonstrated that an intricate link between epithelial-mesenchymal transition （EMT） and anticancer drug resistance in cell culture and animal model. The aim of this study is to further investigate the relationship between chemoresistance and EMT in non-small cell lung cancer （NSCLC） through observing the expression status of EMT markers and resistance protein in histological level. Methods： The resistance protein， excision repair cross-complementing 1 （ERCCl） and EMT markers， including E-cadherin and vimentin， were detected by immunohistochemistry in 100 cases of NSCLC， half of that were treated with pre-operative neoadjuvant chemotherapy （neoadjuvant chemotherapy group）， and the other underwent surgery alone （simple surgery group）. Results： There were significant positive correlations between the expression of ERCCl and vimentin in neoadjuvant chemotherapy group （r = 0.471，P = 0.01） and simple surgery group （ r = 0.380，P = 0.01）， and significant negative correlations between the ERCCl and E-cadherin in neoadjuvant chemotherapy group（r = -0.401，P = 0.01） and simple surgery group （r = -0.295，P = 0.03. In neoadjuvant chemotherapy group， EMT status （p = 0.04） and drug resistance （p = 0.03） were more apparent than simple surgery group. The expression levels of ERCCl， vimentin and E-cadherin were all related to differentiated degree and lymph node metastasis in both groups（P0.05）. 3.2 Correlation between resistance protein and EMT makers To explore whether the development of EMT is correlated with the occurrence of chemoresistance in vivo， we analyzed the expression of ERCC1， vimentin and E-cadherin in tumor tissues. Immunohistochemical findings showed that the expression of ERCC1， vimentin and E-cadherin were 76.0%（38/50）， 64.0%（32/50） and 30.0%（15/50） in neoadjuvant chemotherapy group， and 58.0%（29/50）， 52.0%（26/50） and 32.0%（