Promoter methylation of APC and RAR-β genes as prognostic markers in non-small cell lung cancer (NSCLC)

Aberrant promoter hypermethylations of tumor suppressor genes are promising markers for lung cancer diagnosis and prognosis. The purpose of this study was to determine methylation status at APC and RAR-β promoters in primary NSCLC, and whether they have any relationship with survival. APC and RAR-β promoter methylation status were determined in 41 NSCLC patients using methylation specific PCR. APC promoter methylation was detectable in 9 (22.0%) tumor samples and 6 (14.6%) corresponding non-tumor samples (P = 0.391). RAR-β promoter methylation was detectable in 13 (31.7%) tumor samples and 4 (9.8%) corresponding non-tumor samples (P = 0.049) in the NSCLC patients. APC promoter methylation was found to be associated with T stage (P = 0.046) and nodal status (P = 0.019) in non-tumor samples, and with smoking (P = 0.004) in tumor samples. RAR-β promoter methylation was found associated with age (P = 0.031) in non-tumor samples and with primary tumor site in tumor samples. Patients with APC promoter methylation in tumor samples showed significantly longer survival than patients without it (Log-rank P = 0.014). In a multivariate analysis of prognostic factors, APC methylation in tumor samples was an independent prognostic factor (P = 0.012), as were N1 positive lymph node number (P = 0.025) and N2 positive lymph node number (P = 0.06). Our study shows that RAR-β methylation detected in lung tissue may be used as a predictive marker for NSCLC diagnosis and that APC methylation in tumor sample may be a useful marker for superior survival in NSCLC patients.