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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

  • Authors:
    • Dong Sun Kim
    • Won Kee Lee
    • Jae Yong Park

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  • Published online on: September 5, 2018     https://doi.org/10.3892/ol.2018.9404
  • Pages: 5823-5828

  • Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 (Wrap53α) a newly identified natural antisense transcript 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 transcription 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.
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November-2018
Volume 16 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Kim DS, Lee WK and Park JY: Promoter methylation of Wrap53α, an antisense transcript of p53, is associated with the poor prognosis of patients with non‑small cell lung cancer. Oncol Lett 16: 5823-5828, 2018.
APA
Kim, D.S., Lee, W.K., & Park, J.Y. (2018). 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, 16, 5823-5828. https://doi.org/10.3892/ol.2018.9404
MLA
Kim, D. S., Lee, W. K., Park, J. Y."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 16.5 (2018): 5823-5828.
Chicago
Kim, D. S., Lee, W. K., Park, J. Y."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 16, no. 5 (2018): 5823-5828. https://doi.org/10.3892/ol.2018.9404