title: The role of epithelial-mesenchymal transition and IGF-1R expression in prediction of gefitinib activity as the second-line treatment for advanced nonsmall-cell lung cancer.
abstract: OBJECTIVE
  Except for EGFR gene mutation, there is still lack of predictive factors for gefitinib activity as the second-line treatments for advanced NSCLC with wild-type (WT) EGFR or patients with mutant EGFR but showed poor response. Our purpose was to assess the predictive value of epithelial-mesenchymal transition (EMT) and IGF-1R for gefitinib efficacy as the second-line treatment for NSCLC.
  
  
  METHODS
  53 advanced NSCLC patients who accepted gefitinib as the second-line treatment were enrolled in this study. Expression of E-cadherin, vimentin, and IGF-1R was determined by immunohistochemistry. EGFR gene mutation was determined by liquidchip technique.
  
  
  RESULTS
  The positive rate of EMT, IGF-1R, and EGFR gene mutation was 54.7%, 58.5%, and 39.6%, respectively. EMT (-) was positively correlated with EGFR gene mutation (p = .034) and EMT (+) was associated with IGF-1R (+) (p = .000). EMT (-) was associated with a significantly higher objective response rate (ORR) for all the 53 patients (41.7% vs. 6.9%, p = .024) and showed a higher ORR tendency than EMT (+) in EGFR mutation patients (50.0% vs. 28.6%) and WT EGFR patients (20.0% vs. 4.5%) (p > .05). EMT (-) showed a significant longer median survival time (MST) than EMT (+) for all 53 patients (8 months vs. 4 months) and WT EGFR patients (6 months vs. 3 months) (p < .05). IGF-1R (-) showed a higher ORR tendency than IGF-1R (+) in EGFR mutation patients (54% vs. 30%) and WT EGFR patients (18.2% vs. 4.8%) (p > .05).
  
  
  CONCLUSIONS
  EMT is correlated with efficacy of gefitinib as the second-line treatment for NSCLC, and combined detection of EMT and IGF-1R may be used as new predictors besides EGFR mutation, especially for patients with WT EGFR.
authors.affiliation: Department of Oncology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, Guangdong, P. R. China.
authors.forename: Bei
authors.initials: B
authors.lastname: Chen
authors.forename: Feng
authors.initials: F
authors.lastname: Xiao
authors.forename: Baofeng
authors.initials: B
authors.lastname: Li
authors.forename: Bo
authors.initials: B
authors.lastname: Xie
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
authors.forename: Jihua
authors.initials: J
authors.lastname: Zheng
authors.forename: Weimin
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D000077156:Gefitinib; D018773:Genes, erbB-1 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011799:Quinazolines / Q000627:therapeutic use; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D017526:Receptor, IGF Type 1; D000077156:Gefitinib