Predictive value of unmethylated RASSF1A on disease progression in non-small cell lung cancer patients receiving pemetrexed-based chemotherapy.

BACKGROUND AND OBJECTIVE: Chemotherapy remains the basis of the treatment of lung cancer, and screening biomarkers with predictive value for chemotherapy is of great interest. The present study focused on status of genes methylation in NSCLC patients receiving pemetrexed- or gemcitabine-based chemotherapy. PATIENTS AND METHODS: Promoter methylation of Ras association domain family (RASSF1A) and short stature homeobox 2 (SHOX2) was examined in bronchoalveolar lavage (BAL) from 117 NSCLC patients treated with chemotherapy. Multivariate analysis was used to identify the predictive value of gene methylation. Progression-free survival (PFS) rather than overall survival (OS) was used as the clinical outcome to minimize the impact of chemotherapy on gene methylation. RESULTS: The methylation of RASSF1A and SHOX2 was significantly associated with shorter PFS (RASSF1A: HR = 2.355, 95% CI: 1.533-3.617, P < 0.0001; SHOX2: HR = 2.123, 95% CI: 1.392-3.236, P = 0.0004). After adjusting for confounding factors, RASSF1A methylation was still a predictive factor for PFS (HR = 1.765, 95% CI: 1.064-2.928, P = 0.0278). In the pemetrexed group, unmethylated RASSF1A could be used to predict longer PFS (P = 0.0001), and no predictive value was found in the gemcitabine group. CONCLUSION: Unmethylated RASSF1A is a favorable prognostic indicator for patients receiving pemetrexed doublets. Because of the promoting effect of most chemotherapeutic drugs on gene methylation, unmethylated RASSF1A is not suitable as a predictor for gemcitabine doublets.