Promoter methylation of , 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 ~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 TP53α () a newly identified natural antisense transcript of p53, can regulate p53 expression following DNA damage. The present study determined the methylation status of the 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 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 mutation-negative cases (P=0.08). Methylation of 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, promoter methylation significantly associated with poor overall survival in 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 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.