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

OBJECTIVE
To determine the relation between the promoter methylation status of RUNX3 gene and clinicopathological parameters, prognosis of non-small cell lung cancer (NSCLC).


METHODS
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.


RESULTS
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.


CONCLUSION
RUNX3 methylation is a significant independent prognostic factor for disease-free survival and overall survival.