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Clinicopathological significance and a potential drug target of RARβ in non-small-cell lung carcinoma: a meta-analysis and a systematic review

Authors Song X, Shi K, Zhou S, Yu D, Liu Z, Han Y

Received 21 September 2015

Accepted for publication 8 December 2015

Published 6 April 2016 Volume 2016:10 Pages 1345—1354

DOI https://doi.org/10.2147/DDDT.S96766

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Syed Nasir Abbas Bhukari

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Wei Duan


Xiaoyun Song,* Kang Shi,* Shi-Jie Zhou, Da-Ping Yu, Zhidong Liu, Yi Han

Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China

*These authors contributed equally to this work

Abstract: Lung cancer is the leading cause of cancer-related mortality in men worldwide. Aberrant RARβ promoter methylation has been frequently investigated in non-small-cell lung carcinoma (NSCLC), the most common form of lung cancer. The aim of present study was to carry out a meta-analysis and a systematic review to evaluate clinicopathological significance of RARβ promoter hypermethylation in NSCLC. A systematic literature search was carried out. The data were extracted and assessed by two reviewers independently. The Cochrane software Review Manager 5.2 was used to conduct the review. Odds ratios (ORs) with 95% corresponding confidence intervals (CIs) were calculated. A total of 18 relevant articles were available for meta-analysis which included 1,871 participants. The frequency of RARβ hypermethylation was significantly increased in NSCLC than in nonmalignant lung tissue, and the pooled OR was 5.69 (P<0.00001). RARβ hypermethylation was significantly more frequently observed in adenocarcinoma (AC) than in squamous cell carcinoma (SCC), and the pooled OR was 1.47 (P=0.005). Hypermethylation of RARβ gene in NSCLC was 2.46 times higher in smoking than in nonsmoking individuals, and the pooled OR was 2.46 (P=0.0002). RARβ hypermethylation rate was not significantly correlated with stage of the disease and sex. RARβ gene methylation status was not associated with prognosis of patients with NSCLC. In conclusion, RARβ promoter hypermethylation significantly increased in NSCLC than in non-neoplastic lung tissue and is predominant in AC, suggesting that RARβ methylation contributes to the development of NSCLC, especially AC. RARβ gene is a potential novel target for development of personalized therapy in patients with NSCLC, and is promising in restoration of retinoic acid-target gene induction via demethylation of RARβ1' promoter.

Keywords: NSCLC, RARβ, methylation, tumor suppressor gene, drug target, RA-resistance, meta-analysis, odds ratio

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