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

Xinmei Yang; Lei Yang; Wanrong Dai; Bo Ye

doi:10.2147/OTT.S117161

Role of p14^ARF and p15^INK4B promoter methylation in patients with lung cancer: a systematic meta-analysis

Onco Targets Ther. 2016 Nov 11:9:6977-6985. doi: 10.2147/OTT.S117161. eCollection 2016.

Authors

Xinmei Yang¹, Lei Yang², Wanrong Dai³, Bo Ye⁴

Affiliations

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

Abstract

Background: The cyclin-dependent kinase inhibitors p14^ARF and p15^INK4B are tumor suppressor genes that have been reported to be silenced through promoter methylation in many human cancers. However, the strength of association between p14^ARF or p15^INK4B promoter methylation and lung cancer remains unclear. Thus, we first determined whether p14^ARF and p15^INK4B 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 p14^ARF 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 p15^INK4B promoter methylation and lung cancer (P=0.27). Subgroup analysis of ethnicity revealed that p14^ARF promoter methylation was significantly related to the risk of NSCLC in Asian and Caucasian populations. Subgroup analysis of sample type demonstrated that p14^ARF promoter methylation was correlated with the risk of NSCLC in tissue samples (P<0.001), but not in bronchoalveolar lavage fluid and blood samples. P14^ARF promoter methylation from one study was not significantly correlated with overall survival of patients with NSCLC. Promoter methylation of p14^ARF and p15^INK4B 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 p14^ARF promoter methylation may play an important role in the carcinogenesis of lung cancer, but not p15^INK4B promoter methylation. Promoter methylation of p14^ARF and p15^INK4B was not associated with clinicopathological parameters. However, more extensive large-scale studies are essential to further validate our study.

Keywords: lung cancer; methylation; overall survival; p14ARF; p15INK4B.