RUNX3 promoter hypermethylation and prognosis of early surgically resected non-small cell lung cancers

Abstract

To determine the relation between the promoter methylation status of RUNX3 gene and clinicopathological parameters, prognosis of non-small cell lung cancer (NSCLC). We collected 80 formalin-fixed paraffin-embedded lung cancer tissue samples from NSCLC patients who received postoperative adjuvant chemotherapy with cisplatin. Genomic DNA was extracted through phenol/chloroform extraction. The methylation status of RUNX3 was determined by nested methylation-specific PCR (nMSP). We investigated the pathological and prognostic characteristics of NSCLC stratified by methylation status. The RUNX3 promoter methylation was observed in 20 of the 80 NSCLC samples (25.0%). Methylation of RUNX3 was more frequent in adenocarcinomas (36%) than in squamous cell carcinomas (11%) (P=0.020). In multivariate Logistic regression, positive RUNX3 methylation status (P=0.011) was found to be independent disease-free survival factor as was N stage (P<0.001). Kaplan-Meier curves showed patients with RUNX3 methylation had a significantly poorer overall survival than those without methylation (P=0.003; log-rank test). In multivariate Cox proportional hazards regression analysis, RUNX3 methylation (RR:2.345, 95% CI:1.30-4.865, P=0.022) was a significant independent prognostic factor for the overall survival. RUNX3 methylation is a significant independent prognostic factor for disease-free survival and overall survival.