Expression of the enhancer of zeste homolog 2 in biopsy specimen predicts chemoresistance and survival in advanced non-small cell lung cancer receiving first-line platinum-based chemotherapy.

OBJECTIVES

Enhancer of zeste homolog 2 (EZH2) plays a key role in tumorigenesis and cancer progression through epigenetic gene silencing and chromatin remodeling. The objective of this study was to investigate the correlation between EZH2 expression and platinum-based chemotherapy response as well as survival of patients with advanced non-small cell lung cancer (NSCLC).

MATERIALS AND METHODS

We identified 360 consecutive stage IIIB and IV NSCLC patients who underwent first-line platinum-based chemotherapy. Immunohistochemical analysis of EZH2 on the paraffin-embedded pre-treatment tumor samples was performed and correlated with chemotherapy response and survival.

RESULTS

EZH2 was positive in 204 of 360 patients (56.7%). Of the 204 positive EZH2 patients, 72 (35.3%) responded to chemotherapy with either complete response, or partial remission. Of 156 negative EZH2 patients, 90 (57.7%) exhibited a response to chemotherapy. The difference in response to therapy between positive and negative EZH2 patients was statistically significant (p<0.01). Univariate survival analysis indicated that patients with positive EZH2 had a significantly lower disease-free survival (DFS) and overall survival (OS) than those patients with negative EZH2 expression. Multivariate Cox regression analysis demonstrated that positive EZH2 expression was an independent prognostic factor for both DFS and OS. Kaplan-Meier survival curves further confirmed that positive EZH2 expression correlates with poor survival in NSCLC patients.

CONCLUSIONS

Our results indicate that advanced NSCLC patients with positive expression of EZH2 exhibited resistance to cisplatin-based chemotherapy. EZH2 may be a predictive and prognostic factor for cisplatin-based therapy response and disease survival in advanced NSCLC.