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Promoter methylation of Wrap53α, an antisense transcript of p53, is associated with the poor prognosis of patients with non-small cell lung cancer
Oncology Letters, 2018, 16(5), 5823─5828, DOI: https://doi.org/10.3892/ol.2018.9404
Promoter methylation of Wrap53α, an antisense tran of p53, is associated with the poor prognosis of patients with non-small cell lung cancer
Dong Sun Kim, Lee WK; Park JY
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 tranional regulation are still not well defined. WD repeat containing antisense to TP53α (Wrap53α) a newly identified natural antisense tran of p53, can regulate p53 expression following DNA damage. The present study determined the methylation status of the Wrap53α 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 Wrap53α promoter was methylated in 12 (8.2%) of 146 malignant tissues. Its methylation was associated with the downregulation of its tranion and was frequently detected in patients with stages II-IIIA (P=0.03), and p53 mutation-negative cases (P=0.08). Methylation of Wrap53α 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, Wrap53α 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 Wrap53α 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.
- DOI: https://doi.org/10.3892/ol.2018.9404
- ISBN or ISSN: 1792-1074
- 본 연구는 질병관리본부 연구개발과제(과제번호 2018-보건의료생물자원종합관리) 연구비를 지원받아 수행되었습니다.
- This research was supported by a fund(code 2018-보건의료생물자원종합관리) by Research of Korea Centers for Disease Control and Prevention.
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