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

Cancer Invest. 2013 Aug;31(7):454-60. doi: 10.3109/07357907.2013.820315.

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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Carcinoma, Non-Small-Cell Lung* / mortality
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Disease-Free Survival
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gefitinib
  • Genes, erbB-1 / genetics
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Mutation
  • Quinazolines / therapeutic use
  • Receptor, IGF Type 1 / biosynthesis*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Quinazolines
  • Receptor, IGF Type 1
  • Gefitinib