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Role of p14ARF and p15INK4B promoter methylation in patients with lung cancer: a systematic meta-analysis

Authors Yang X, Yang L, Dai W, Ye B

Received 13 July 2016

Accepted for publication 31 August 2016

Published 11 November 2016 Volume 2016:9 Pages 6977—6985

DOI https://doi.org/10.2147/OTT.S117161

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 3

Editor who approved publication: Dr XuYu Yang


Xinmei Yang,1,* Lei Yang,2,* Wanrong Dai,3 Bo Ye4

1Department of Oncology, the First Affiliated Hospital of Jiaxing University, Jiaxing, 2Cancer Center, The First Hospital of Jilin University, Changchun, 3Department of Pharmacy, The First Affiliated Hospital, Zhejiang University, Zhejiang, 4Department of Thoracic Surgery, Hangzhou Red Cross Hospital, Hangzhou, People’s Republic of China

*These authors contributed equally to this work

Background: The cyclin-dependent kinase inhibitors p14ARF and p15INK4B are tumor suppressor genes that have been reported to be silenced through promoter methylation in many human cancers. However, the strength of association between p14ARF or p15INK4B promoter methylation and lung cancer remains unclear. Thus, we first determined whether p14ARF and p15INK4B promoter methylation played a key role in the carcinogenesis of lung cancer.
Methods: Eligible studies were selected from the online electronic databases. The pooled odds ratios or hazard ratios and 95% confidence intervals were calculated and summarized.
Results: Finally, 12 studies with 625 lung cancer samples and 488 nontumor samples were included under the fixed-effects model. The pooled odds ratio showed that p14ARF promoter methylation was observed to be significantly higher in non-small-cell lung cancer (NSCLC) than in nontumor samples (P<0.001). No significant correlation was found between p15INK4B promoter methylation and lung cancer (P=0.27). Subgroup analysis of ethnicity revealed that p14ARF promoter methylation was significantly related to the risk of NSCLC in Asian and Caucasian populations. Subgroup analysis of sample type demonstrated that p14ARF promoter methylation was correlated with the risk of NSCLC in tissue samples (P<0.001), but not in bronchoalveolar lavage fluid and blood samples. P14ARF promoter methylation from one study was not significantly correlated with overall survival of patients with NSCLC. Promoter methylation of p14ARF and p15INK4B was not correlated with clinicopathological characteristics, such as gender status, smoking status, tumor differentiation, and tumor stage (P>0.05).
Conclusion: Our findings suggested that p14ARF promoter methylation may play an important role in the carcinogenesis of lung cancer, but not p15INK4B promoter methylation. Promoter methylation of p14ARF and p15INK4B was not associated with clinicopathological parameters. However, more extensive large-scale studies are essential to further validate our study.

Keywords: p14ARF, p15INK4B, methylation, lung cancer, overall survival

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