Death-associated protein kinase promoter methylation correlates with clinicopathological and prognostic features in nonsmall cell lung cancer patients: A cohort study.

Abstract

The objective was to study the correlation between death-associated protein kinase (DAPK) promoter methylation and the clinicopathological and prognostic features in nonsmall cell lung cancer (NSCLC) patients. A total of 117 NSCLC patients were recruited into our study between December 2012 and December 2014. Methylation-specific polymerase chain reaction was employed to detect the methylation status of DAPK in cancer tissues, peficancerous tissues, and serum samples of 117 NSCLC patients. In addition, serum samples of 115 healthy subjects were analyzed as controls. A literature search of English and Chinese databases, based on predefined criteria, identified published studies closely related to this study. Data were extracted, and meta-analysis was performed using STATA 12.0 software (STATA Corporation, College Station, TX, USA). Our study results showed that DAPK promoter methylation frequency was significantly higher in NSCLC tissues compared to peficancerous normal tissues (58.1% vs. 12.8%, χ2 = 52.45, P < 0.001). When serum samples were compared, DAPK methylation frequency in NSCLC patients was higher than the control group (27.4% vs. 0, χ2 = 37.07, P < 0.001). Our meta-analysis results demonstrated that DAPK methylation frequency was lower in tumor node metastasis (TNM) stage I-II compared to TNM stage III-IV (relative risk [RR] =0.87, 95% confidence interval [CI] =0.76-0.99, P = 0.041). DAPK promoter methylation frequency in NSCLC patients with lymph node metastasis was significantly higher compared to the patients with no metastases (RR = 1.26, 95% CI = 1.04-1.52, P = 0.020). Finally, the 5-year survival rate was lower in NSCLC patient group with high frequency of DAPK methylation, compared to the patient group with unmethylated DAPK (RR = 0.71, 95% CI = 0.56-0.89, P = 0.004). Our results showed that DAPK promoter methylation is tightly correlated with clinicopathological features of NSCLC and is associated with poor prognosis in patients.