Promoter methylation of Wrap53 alpha, an antisense transcript of p53, is associated with the poor prognosis of patients with non-small cell lung cancer

Lung cancer, of which non-small cell lung cancer (NSCLC) accounts for similar to 85% of cases, remains a leading cause of cancer-associated mortality and morbidity worldwide. Tumor suppressor p53 is a master regulator of diverse cellular processes and is a therapeutic target in cancer. However, many aspects of its transcriptional regulation are still not well defined. WD repeat containing antisense to TP53 alpha (Wrap53 alpha) a newly identified natural antisense transcript of p53, can regulate p53 expression following DNA damage. The present study determined the methylation status of the Wrap53 alpha promoter in primary lung tissues using methylation-specific polymerase chain reaction and evaluated its associations with clinicopathological features and survival in patients with NSCLC. The Wrap53 alpha promoter was methylated in 12 (8.2%) of 146 malignant tissues. Its methylation was associated with the downregulation of its transcription and was frequently detected in patients with stages II-IIIA (P=0.03), and p53 mutation-negative cases (P=0.08). Methylation of Wrap53 alpha promoter was associated with worse overall survival of total patients with a borderline significance [adjusted Hazard Ratio (HR)=2.44, 95% Confidence Interval (CI)=0.98-6.04, P=0.05]. Notably, Wrap53 alpha promoter methylation significantly associated with poor overall survival in p53 mutation-negative patients (log-rank P=0.01, adjusted HR=2.92, 95% CI=1.00-8.60, P=0.05), but not in patients with p53 mutations. The results of the present study suggest that Wrap53 alpha may serve a role in the pathogenesis of a subset of lung cancer, and its methylation may be considered to be a prognostic marker for surgically resected NSCLC patients. However, further studies with a larger sample size are required to confirm this finding.