title: DOK2 as a marker of poor prognosis of patients with gastric adenocarcinoma after curative resection.
abstract: BACKGROUND
  DOK2 is known as the substrate of chmeric p210bcr/abl oncoprotein characterizing chronic myelogenous leukemia with Philadelphia chromosome. Reduced DOK2 expression was recently reported in lung adenocarcinoma, suggesting that this protein acts as a tumor suppressor in solid tumors. The purpose of this study was to determine the significance of DOK2 in gastric cancer.
  
  
  METHODS
  The study subjects were 118 patients who underwent curative surgery for gastric cancer, as well as 7 gastric cancer cell lines. The tissues and cell lines were analyzed for DOK2 gene and protein expressions by histopathology and immunohistochemistry, and also using a microsatellite marker for loss of heterozygosity. Correlation of survival with clinicopathological parameters was investigated by univariate and multivariate analyses.
  
  
  RESULTS
  DOK2 expression was confirmed in the normal gastric mucosa. Considerable differences in the gene expression were noted among the gastric cell lines. Positive DOK2 expression was noted in the noncancerous regions of all pathological specimens, whereas 59 (50.0%) specimens of 118 patients were negatively stained in the tumor. Loss of heterozygosity was observed in 54.5% of DOK2(-) cases. DOK2(-) patients were more likely to develop recurrence than DOK2(+) and showed poorer 5-year overall survival (59.1%) than DOK2(+) (76.4%, P = .0403). Multivariate analysis identified pT (hazard ratio [HR] = 2.748, 95% confidence interval [95% CI] = 1.061-8.927, P = .0361), pN (HR = 2.486, 95% CI = 1.264-4.932, P = .0086), and DOK2(-) (HR = 2.343, 95% CI = 1.211-4.727, P = .0112) as significant and independent determinants of poor survival.
  
  
  CONCLUSIONS
  Our data suggest the potential usefulness of DOK2 as a marker of poor prognosis in patients with gastric cancer after curative resection.
authors: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: Hiromichi
authors: H
authors: Miyagaki
authors: Makoto
authors: M
authors: Yamasaki
authors: Tsuyoshi
authors: T
authors: Takahashi
authors: Yukinori
authors: Y
authors: Kurokawa
authors: Hiroshi
authors: H
authors: Miyata
authors: Kiyokazu
authors: K
authors: Nakajima
authors: Shuji
authors: S
authors: Takiguchi
authors: Yoshiyuki
authors: Y
authors: Fujiwara
authors: Masaki
authors: M
authors: Mori
authors: Yuichiro
authors: Y
authors: Doki
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis* / Q000235:genetics; D000230:Adenocarcinoma / Q000737:chemistry* / Q000175:diagnosis / Q000473:pathology / Q000556:secondary / Q000601:surgery*; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001859:Bone Neoplasms / Q000556:secondary; D001932:Brain Neoplasms / Q000556:secondary; D005260:Female; D005500:Follow-Up Studies; D005753:Gastric Mucosa / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000556:secondary; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D009367:Neoplasm Staging; D010750:Phosphoproteins / Q000032:analysis* / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000175:diagnosis / Q000473:pathology / Q000601:surgery*; D016896:Treatment Outcome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C115089:DOK2 protein, human; D010750:Phosphoproteins; D012333:RNA, Messenger