title: Aberrant loss of dickkopf-3 in gastric cancer: can it predict lymph node metastasis preoperatively?
abstract: BACKGROUND
  Dickkopf-3 (DKK3) may act as a tumor suppressor as it is down-regulated in various types of cancer. This study assessed the DKK3 protein expression in gastric cancer and its potential value as a prognostic marker.
  
  
  METHODS
  DKK3 expression was evaluated by immunohistochemistry in 158 gastric cancer samples from patients who underwent gastrectomy from 2002 to 2008. Clinicopathological parameters and survival data were analyzed.
  
  
  RESULTS
  Loss of DKK3 expression was found in 64 of 158 (40.5%) samples, and it was associated with advanced T stage (p < 0.001), lymph node metastasis (p < 0.001), UICC TNM stage (p < 0.001), tumor location (p = 0.029), lymphovascular invasion (p = 0.035), and perineural invasion (p = 0.032). Patients without DKK3 expression in tumor cells had a significantly worse disease-free and overall survival than those with DKK3 expression (p < 0.001, and p = 0.001, respectively). TNM stage (p = 0.028 and p < 0.001, respectively) and residual tumor (p < 0.001 and p = 0.003, respectively) were independent predictors of disease-free and overall survival. Based on the preoperative clinical stage assessed by computed tomography (CT), loss of DKK3 expression was predominantly associated with worse prognosis in patients with clinically node-negative advanced gastric cancer (AGC). The combination of DKK3 expression status and CT increased the accuracy of CT staging for predicting lymph node involvement from 71.5 to 80.0% in AGC patients.
  
  
  CONCLUSIONS
  Loss of DKK3 protein expression was significantly associated with poor survival in patients with gastric cancer and was strongly correlated with the TNM stage. DKK3 might be a potential biomarker of lymph node involvement that can improve the predictive power of CT.
authors.affiliation: Department of Surgery, Chung-Ang University College of Medicine, Seoul, Korea, jmpark@cau.ac.kr.
authors.forename: Joong-Min
authors.initials: JM
authors.lastname: Park
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Kim
authors.forename: Kyong-Choun
authors.initials: KC
authors.lastname: Chi
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Kim
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary* / Q000601:surgery; D000368:Aged; D018925:Chemokines; D018572:Disease-Free Survival; D005260:Female; D005743:Gastrectomy; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D057234:Preoperative Period; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D015996:Survival Rate; D014057:Tomography, X-Ray Computed
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins