title: Promoter hypermethylation of Wnt inhibitory factor-1 in patients with lung cancer: A systematic meta-analysis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou Department of Oncology, the First Affiliated Hospital of Jiaxing University Department of Radiotherapy, People's Hospital of Zhejiang Province, Hangzhou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zheng
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Yiming
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yufen
authors.initials: Y
authors.lastname: Xu
authors.forename: Binbin
authors.initials: B
authors.lastname: Song
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhou
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Liang
authors.forename: Xinmei
authors.initials: X
authors.lastname: Yang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000503:physiopathology; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics; D055752:Small Cell Lung Carcinoma / Q000235:genetics* / Q000503:physiopathology; D051155:Wnt1 Protein / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D012097:Repressor Proteins; C485569:WIF1 protein, human; C495247:WNT1 protein, human; D051155:Wnt1 Protein