title: Plasma DNA methylation of Wnt antagonists predicts recurrence of esophageal squamous cell carcinoma.
abstract: OBJECTIVE
  To detect the effects of plasma DNA methylation of Wnt antagonists/inhibitors on recurrence of esophageal squamous cell carcinoma (ESCC).
  
  
  METHODS
  We used methylation-specific polymerase chain reaction to detect hypermethylation of the promoter of four Wnt antagonists/inhibitors (SFRP-1, WIF-1, DKK-3 and RUNX3) using DNA from the plasma of ESCC patients (n = 81) and analyzed the association between promoter hypermethylation of Wnt pathway modulator genes and the two-year recurrence of ESCC.
  
  
  RESULTS
  Hypermethylation of SFRP-1, DKK-3 and RUNX-3 was significantly associated with an increased risk of ESCC recurrence (P = 0.001, 0.003 and 0.001 for SFRP-1, DKK-3 and RUNX3, respectively). Patients carrying two to three methylated genes had a significantly elevated risk of recurrence compared with those not carrying methylated genes (odds ratio = 15.69, 95% confidential interval: 2.97-83). The area under the receiver operating characteristic curve (AUC) was 77.1 for ESCC recurrence prediction (sensitivity = 66.67 and specificity = 83.3). When combining methylated genes and the clinical stage, the AUC was 83.69, with a sensitivity of 76.19 and a specificity of 83.3.
  
  
  CONCLUSIONS
  The status of promoter hypermethylation of Wnt antagonists/inhibitors in plasma may serve as a non-invasive prognostic biomarker for ESCC.
authors.affiliation: Institute of Life Science, Jiangsu University, Zhenjiang 212013, Jiangsu Province, China.
authors.forename: Ji-Bin
authors.initials: JB
authors.lastname: Liu
authors.forename: Fu-Lin
authors.initials: FL
authors.lastname: Qiang
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.forename: Jin
authors.initials: J
authors.lastname: Cai
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Zhou
authors.forename: Min-Xin
authors.initials: MX
authors.lastname: Shi
authors.forename: Ke-Ping
authors.initials: KP
authors.lastname: Chen
authors.forename: Zhi-Bin
authors.initials: ZB
authors.lastname: Hu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control*; D018925:Chemokines; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012372:ROC Curve; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D055502:Secondary Prevention; D051153:Wnt Proteins / Q000037:antagonists & inhibitors*; D060449:Wnt Signaling Pathway / Q000502:physiology; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D018925:Chemokines; D050677:Core Binding Factor Alpha 3 Subunit; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012097:Repressor Proteins; D051153:Wnt Proteins; C498624:DKK3 protein, human; C493729:Runx3 protein, human; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins; C485569:WIF1 protein, human