title: Integrated Epigenomics Analysis Reveals a DNA Methylation Panel for Endometrial Cancer Detection Using Cervical Scrapings.
abstract: OBJECTIVE
  Endometrial cancer is a common gynecologic cancer whose incidence is increasing annually worldwide. Current methods to detect endometrial cancer are unreliable and biomarkers are unsatisfactory for screening. Cervical scrapings were reported as a potential source of material for molecular testing. DNA methylation is a promising cancer biomarker, but limited use for detecting endometrial cancer.
  
  
  METHODS
  We analyzed two methylomics databases of endometrioid-type endometrial cancer. Using nonnegative matrix factorization algorithm clustered the methylation pattern and reduced the candidate genes. We verified in pools DNA from endometrial cancer tissues and cervical scrapings, and validated in 146 cervical scrapings from patients with endometrioid-type endometrial cancer (n = 50), uterine myoma (n = 40), and healthy controls (n = 56) using quantitative methylation-specific PCR (QMSP). The logistic regression was used to evaluate the performance of methylation signal and gene combination.
  
  
  RESULTS
  We filtered out 180 methylated genes, which constituted four consensus clusters. Serial testing of tissues and cervical scrapings detected 14 genes that are hypermethylated in endometrial cancer. Three genes, BHLHE22, CDO1, and CELF4, had the best performance. Individual genes were sensitivity of 83.7%-96.0% and specificity of 78.7%-96.0%. A panel comprising any two of the three hypermethylated genes reached a sensitivity of 91.8%, specificity of 95.5%, and odds ratio of 236.3 (95% confidence interval, 56.4-989.6). These markers were also applied to cervical scrapings of type II endometrial cancer patients, and detected in 13 of 14 patients.
  
  
  CONCLUSIONS
  This study demonstrates the potential use of methylated BHLHE22/CDO1/CELF4 panel for endometrial cancer screening of cervical scrapings. Clin Cancer Res; 23(1); 263-72. ©2016 AACR.
authors: Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, New Taipei, Taiwan.
authors: Rui-Lan
authors: RL
authors: Huang
authors: Translational epigenetic center, Shuang Ho Hospital, Taipei Medical University, New Taipei, Taiwan.
authors: Po-Hsuan
authors: PH
authors: Su
authors: Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors: Yu-Ping
authors: YP
authors: Liao
authors: Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Obstetrics and Gynecology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors: Tzu-I
authors: TI
authors: Wu
authors: Molecular Medicine, University of Texas, Health Science Center, San Antonio, Texas.
authors: Ya-Ting
authors: YT
authors: Hsu
authors: Department of Public Health and Primary Care, Cardiovascular Epidemiology Unit, Strangeways Research Laboratory, University of Cambridge, Cambridge, United Kingdom.
authors: Wei-Yu
authors: WY
authors: Lin
authors: Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors: Hui-Chen
authors: HC
authors: Wang
authors: Translational epigenetic center, Shuang Ho Hospital, Taipei Medical University, New Taipei, Taiwan.
authors: Yu-Chun
authors: YC
authors: Weng
authors: Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors: Yu-Che
authors: YC
authors: Ou
authors: Molecular Medicine, University of Texas, Health Science Center, San Antonio, Texas.|Cancer Therapy and Research Center and Departments, University of Texas, Health Science Center, San Antonio, Texas.
authors: Tim Hui-Ming
authors: TH
authors: Huang
authors: Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, New Taipei, Taiwan. hclai@s.tmu.edu.tw hclai30656@gmail.com.|Translational epigenetic center, Shuang Ho Hospital, Taipei Medical University, New Taipei, Taiwan.|Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Department and Graduate Institute of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
authors: Hung-Cheng
authors: HC
authors: Lai
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D016022:Case-Control Studies; D016000:Cluster Analysis; D018899:CpG Islands; D019175:DNA Methylation; D016889:Endometrial Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D057890:Epigenomics / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D012372:ROC Curve; D015203:Reproducibility of Results
chemical_list: D014408:Biomarkers, Tumor