title: Dickkopf-1 expression as a marker for predicting clinical outcome in esophageal squamous cell carcinoma.
abstract: OBJECTIVE
  Dickkopf-1 (DKK1) is the inhibitor of the canonical Wnt signaling pathway, however it is highly transactivated in various cancers, suggesting the presence of unknown mechanism. Its implication in human esophageal squamous cell carcinoma (ESCC) has not been sufficiently investigated.
  
  
  METHODS
  We evaluated DKK1 protein expression in resected specimens from 170 patients with ESCC by immunohistochemistry. Tumors were categorized as positive or negative for DKK1. The relationships between DKK1 expression in ESCC and various clinicopathological parameters and prognosis (disease-free survival; DFS) were analyzed separately.
  
  
  RESULTS
  Immunohistochemically, 72 (42.4%) tumors were DKK1 positive while no significant staining was observed in the normal squamous epithelium except for few basal cells. There was no significant relationship between DKK1 expression in ESCC and any of the clinicopathological parameters tested in this study. Patients with DKK1-positive tumors had poorer DFS than those with negative ESCC (5-year DFS; 31.5% versus 53.6%, P = 0.0062). Univariate analysis showed a significant relationship between pT [hazard ratio (HR) = 2.944, 95% confidence interval (CI) = 1.713-5.059, P < 0.0001], number of pN (HR = 2.836, 95% CI = 1.866-4.309, P < 0.0001), lymphatic invasion (HR = 2.892, 95% CI = 1.336-6.262, P = 0.0070), and DKK1 expression (HR = 1.763, 95% CI = 1.167-2.663, P = 0.0071) and DFS. Multivariate analysis including the above four parameters identified pT (HR = 2.053, 95% CI = 1.157-3.645, P = 0.0140), pN number (HR = 2.107, 95% CI = 1.362-3.260, P = 0.0008), and DKK1 expression (HR = 1.813, 95% CI = 1.195-2.751, P = 0.0052) as independent and significant prognostic factors for DFS.
  
  
  CONCLUSIONS
  Our data suggest the usefulness of DKK1 as a novel predictor of poor prognosis of patients with ESCC after curative resection and also as a therapeutic target for future tailored therapies against ESCC.
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Makino
authors.forename: Makoto
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takemasa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takeno
authors.forename: Yurika
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyata
authors.forename: Shuji
authors.initials: S
authors.lastname: Takiguchi
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Nariaki
authors.initials: N
authors.lastname: Matsuura
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins