Promoter hypermethylation of Wnt inhibitory factor-1 in patients with lung cancer: A systematic meta-analysis

• Published in: Medicine (Baltimore) Vol. 95; no. 49; p. e5433
• Main Authors: Zheng, Yu, Li, Xia, Jiang, Yiming, Xu, Yufen, Song, Binbin, Zhou, Qiang, Liang, Xiaodong, Yang, Xinmei
• Format: Journal Article
• Language: English
• Published: United States The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved 01.12.2016; Wolters Kluwer Health
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - physiopathology; DNA Methylation; Female; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease - epidemiology; Humans; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Lung Neoplasms - physiopathology; Male; Prognosis; Promoter Regions, Genetic; Repressor Proteins - genetics; Small Cell Lung Carcinoma - genetics; Small Cell Lung Carcinoma - physiopathology; Systematic Review and Meta-Analysis; Wnt1 Protein - genetics
• ISSN: 0025-7974; 1536-5964; 1536-5964
• DOI: 10.1097/MD.0000000000005433

Promoter hypermethylation of Wnt inhibitory factor-1 (WIF-1)-a tumor suppressor gene-has been detected in several types of human tumors. However, the association between WIF-1 promoter hypermethylation and lung cancer remains to be elucidated. Therefore, we conducted this study to evaluate the clinical significance of WIF-1 promoter hypermethylation in lung cancer. A comprehensive literature search was conducted to obtain eligible studies. The combined odds ratios (ORs) or hazard ratios and 95% confidence intervals were used to estimate the strength of associations. A total of 8 eligible publications with 626 cases and 512 controls were included in our study. The combined ORs revealed that WIF-1 promoter hypermethylation was significantly higher in lung cancer than in controls (OR 10.53, P < 0.001). Moreover, WIF-1 promoter hypermethylation was significantly associated with smoking behavior (OR 1.88, P = 0.002). No significant correlation was found between WIF-1 promoter hypermethylation and sex status, age status, tumor stage, and pathological types in cancer. Multivariate analysis results indicated the absence of correlation between WIF-1 promoter hypermethylation and with relapse-free survival and overall survival. Subgroup analysis by sample type demonstrated that promoter hypermethylation of WIF-1 was significantly associated with an increased risk of lung cancer in the tissue (OR 7.89, P < 0.001), blood (OR 21.83, P = 0.034), and pleural effusion subgroups (OR 157.43, P = 0.001). Promoter hypermethylation of WIF-1 may play a crucial role in lung cancer carcinogenesis. It may be a noninvasive biomarker using blood or pleural effusion detection. WIF-1 promoter hypermethylation is correlated with smoking behavior, but not with sex status, age status, tumor stage, pathological types, and the prognosis of lung cancer patients in terms of relapse-free survival and overall survival. More investigations, including a larger number of subjects, are required to further confirm the findings of our analysis.