title: Meta-analysis demonstrates no association between p16ink4apromoter methylation and epithelial ovarian cancer.
abstract: BACKGROUND
  p16INK4A(p16) functions as a tumor suppressor gene in various malignancies. Aberrant p16 methylation has been proposed to be essential in ovarian carcinogenesis. However, it is unclear whether p16 can be used as a diagnostic marker owing to the small sample sizes in previous studies.
  
  
  METHODS
  To determine whether p16 promoter methylation is associated with epithelial ovarian cancer and can thus be used as a diagnostic marker, we performed a meta-analysis of published studies. The following databases were searched using a systematic search method: PubMed, Web of Science, EMBASE, and Chinese National Knowledge Infrastructure. We used a random-effects model to analyze the relative risk (RR); we also evaluated between-study heterogeneity, subgroup heterogeneity, and publication bias.
  
  
  RESULTS
  Our meta-analysis included eight eligible studies, with 428 ovarian cancers and 278 normal tissue samples and benign neoplasms. p16 promoter methylation was identified in 5.4 to 43.2% (median 27.86%) of ovarian cancers and 0 to 37.5% (median 15.8%) of normal tissue and benign neoplasms indicating that no significant association exists between p16 promoter methylation and epithelial ovarian cancer. However, the pooled results also showed that the RR was 1.52 (95% CI 0.80-2.87) in the ovarian cancer cases versus the corresponding normal and benign cases under the random-effects model. Between-study heterogeneity was determined through a sensitivity analysis; the I2value did not change when one study was excluded.
  
  
  CONCLUSIONS
  Our study showed that p16 promoter methylation cannot be used to differentiate benign from malignant epithelial ovarian tumors. Therefore, p16 promoter methylation cannot be used as a marker for diagnosing the early stage of ovarian cancer.
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.|Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.|Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
authors.forename: Fangrong
authors.initials: F
authors.lastname: Yan
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, China.
authors.forename: Yicong
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, China. wenjuncheng117@gmail.com.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Cheng
mesh_terms: D000077216:Carcinoma, Ovarian Epithelial; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D011401:Promoter Regions, Genetic
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16
keywords: Meta-analysis; Methylation; Ovarian cancer; p16