title: Quantitative assessment of the diagnostic role of APC promoter methylation in non-small cell lung cancer.
abstract: BACKGROUND
  Adenomatous polyposis coli (APC) has been reported to be a candidate tumor suppressor in many cancers. However, the diagnostic role of APC promoter methylation in non-small cell lung cancer (NSCLC) remains unclear. We systematically integrated published articles and DNA methylation microarray data to investigate the diagnostic performance of the APC methylation test for NSCLC. Two thousand two hundred and fifty-nine NSCLC tumor samples and 1,039 controls were collected from 17 published studies and TCGA NSCLC data. The association between APC promoter methylation and NSCLC was evaluated in a meta-analysis. An independent DNA methylation microarray dataset from TCGA project, in which five CpG sites located in the promoter region of APC were involved, was used to validate the results of the meta-analysis.
  
  
  RESULTS
  A significant association was observed between APC promoter hypermethylation and NSCLC, with an aggregated odds ratio (OR) of 3.79 (95% CI: 2.22 to 6.45) in a random effects model. Pooled sensitivity and specificity were 0.548 (95% CI: 0.42 to 0.67, P < 0.0001) and 0.776 (95% CI: 0.62 to 0.88, P < 0.0001), respectively. Each of the five CpG sites was much better in prediction (area under the curve, AUC: 0.71 to 0.73) in lung adenocarcinoma (Ad) than in lung squamous cell carcinoma (Sc) (AUC: 0.45 to 0.61). The AUCs of the logistic prediction model based on these five CpGs were 0.73 and 0.60 for Ad and Sc, respectively. Integrated analysis indicated that CpG site location, heterogeneous or autogenous controls, and the proportion of adenocarcinoma in samples were the most significant heterogeneity sources.
  
  
  CONCLUSIONS
  The methylation status of APC promoter was strongly associated with NSCLC, especially adenocarcinoma. The APC methylation test could be applied in the clinical diagnosis of lung adenocarcinoma.
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Shicheng
authors.initials: S
authors.lastname: Guo
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Lixing
authors.initials: L
authors.lastname: Tan
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Weilin
authors.initials: W
authors.lastname: Pu
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China.|Department of Pneumology, Changhai Hospital of Shanghai, Second Military Medical University, Shanghai 200433, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Head and Neck Surgery, Cancer Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Kuan
authors.initials: K
authors.lastname: Xu
authors.affiliation: Department of General Surgery, University of Qingdao Affiliated Hospital of Medical College, Qingdao University, 1677 Wutaishan Street, Qingdao City 266071, China.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Pneumology, Changhai Hospital of Shanghai, Second Military Medical University, Shanghai 200433, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Yanyun
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Cardiothoracic Surgery, Changhai Hospital of Shanghai, Second Military Medical University, Shanghai, China.
authors.forename: Jibin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Jiucun
authors.initials: J
authors.lastname: Wang