The aim of the present study was to assess the expression of epithelial-mesenchymal transition
biomarkers (
E-cadherin and
vimentin) and their potential significance as prognostic markers in patients with stage IIIB/IV non-squamous
non-small cell lung cancer (NSCLC) enrolled in the INNOVATIONS trial, receiving treatment with either
erlotinib/
bevacizumab (EB) or
cisplatin/
gemcitabine/
bevacizumab (
PGB). The
tumor tissues of 104 patients were retrospectively analyzed using immunohistochemistry to assess the expression of
E-cadherin and
vimentin. The distribution between the treatment arms was 46 patients in the EB-arm and 58 in the
PGB-arm. Comparing the treatment arms according to
E-cadherin and
vimentin expression, the analysis revealed that progression-free survival (PFS) was increased in the
PGB treatment group when compared with EB treatment in patients with low expression of
E-cadherin [hazard ratio (HR)=0.353; 95% confidence interval (CI) 0.189- 0.658; log-rank P=0.0007] and in those with high expression of
vimentin [HR=0.276 (95% CI, 0.115- 0.659), log-rank P=0.0021]. In patients that exhibited high
E-cadherin and were negative for
vimentin, there was no difference in the PFS between the
PGB and EB treatment groups. In conclusion, in non-squamous NSCLC with downregulated
E-cadherin and upregulated
vimentin, the efficacy of
chemotherapy with
PGB was superior compared with EB; but the same effect was not observed in patients with high
E-cadherin and low
vimentin. Although increased PFS was observed in patients with
PGB treatment compared with EB treatment in the whole analysis populations, in the subgroup of patients with the mesenchymal phenotype, no prognostic or predictive value of either
biomarker could be identified. The potential role of
bevacizumab in overcoming
chemotherapy resistance in the population with the mesenchymal phenotype has to be further explored.