title: Upregulated expression of DIXDC1 in intestinal-type gastric carcinoma: co-localization with β-catenin and correlation with poor prognosis.
abstract: BACKGROUND
  DIXDC1 (Dishevelled-Axin domain containing 1) is a positive regulator of the Wnt pathway. In the field of cancer research, the role of DIXDC1 is unclear. Our previous in vitro study showed that DIXDC1 enhances β-catenin nuclear accumulation in gastric cancer cell lines. The aim of this study was to detect the expression of DIXDC1 in different histological subtypes of gastric carcinoma and to evaluate the correlation between the expression of DIXDC1 and β-catenin localization and clinicopathological parameters, including patients' survival.
  
  
  METHODS
  Immunohistochemical staining was performed to characterize the expression of DIXDC1 and β-catenin in archived materials from 259 cases of gastric carcinoma. The χ2 test and the Fisher's test were used to analyze correlations between DIXDC1 expression, β-catenin localization, and clinicopathological parameters. Univariate analyses were performed using the Kaplan-Meier method, and the survival difference between groups was assessed by the log-rank test. Multivariate analysis was performed using the Cox proportional hazards regression model.
  
  
  RESULTS
  Positive DIXDC1 staining was detected in tumor cells in 123 of 259 (47.5 %) cases. DIXDC1 expression in gastric carcinoma was significantly correlated with the histological intestinal-type (P < 0.001), the depth of tumor invasion (P < 0.001) and the lymph node metastasis (P = 0.006). In the intestinal-type, DIXDC1 was correlated with the nuclear and cytoplasmic β-catenin expression (P = 0.002). Kaplan-Meier analysis indicated that patients with high DIXDC1 expression had poor disease-specific survival (P < 0.001), especially in the intestinal-type. Moreover, multivariate regression analysis showed that positive expression of DIXDC1 was an independent prognostic predictor of intestinal-type gastric carcinoma.
  
  
  CONCLUSIONS
  Our study indicated that DIXDC1 is a significant independent prognostic indicator in intestinal-type gastric carcinoma that plays an important role in carcinogenesis and progression of gastric carcinoma through the Wnt signaling pathway.
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032 China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032 China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China.
authors.forename: Cong
authors.initials: C
authors.lastname: Tan
authors.affiliation: Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433 China.
authors.forename: Fan
authors.initials: F
authors.lastname: Qiao
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032 China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China.
authors.forename: Weige
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032 China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China.
authors.forename: Xiangnan
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032 China.
authors.forename: Peng
authors.initials: P
authors.lastname: Lian
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032 China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China.
authors.forename: Bin
authors.initials: B
authors.lastname: Chang
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032 China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Sheng
keywords: DIXDC1; Gastric carcinoma; Immunohistochemistry; Intestinal-type; β-catenin