title: Notch1 activation is a poor prognostic factor in patients with gastric cancer.
abstract: BACKGROUND
  Aberrant Notch1 activation has been studied in many malignant tumours, but its role in gastric cancer remains unknown. This study is aimed to investigate the prognostic significance of Notch1 activation in patients with gastric cancer.
  
  
  METHODS
  In this study, we prospectively enrolled two independent sets of patients with gastric cancer from China and defined the activation of Notch1 by immunohistochemical staining of its active form, intracellular domain of Notch1 (ICN1). The prognostic value of Notch1 activation and clinical outcomes in gastric cancer were evaluated.
  
  
  RESULTS
  Expression of ICN1 is elevated in gastric cancer tissues and is predominately localised in the cell cytoplasm and/or membrane. High ICN1 expression positively correlates with tumour invasion depth (P=0.032), lymph node metastasis (P<0.001), advanced TNM stage (P=0.003) and reduced overall survival (P=0.0004) in the training set. Multivariate Cox regression analysis identified ICN1 as an independent prognostic factor (P=0.031), which could be incorporated into the TNM system to generate a better predictive model for patient outcomes. The c-index was 0.7375 when assessed with the TNM stage and improved to 0.8037 when ICN1 expression was added in the training set. These results were validated in the validation set.
  
  
  CONCLUSIONS
  Notch1 activation was correlated with gastric cancer progression and defined as a novel independent prognostic factor. Combining ICN1 expression with TNM stage may provide a better predictive model for outcomes of gastric cancer patients.
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai 200032, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai 200032, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Glycoconjugate Research, MOH, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, China.
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai 200032, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
mesh_terms: D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D017434:Protein Structure, Tertiary; D051881:Receptor, Notch1 / Q000819:agonists* / Q000737:chemistry; D013274:Stomach Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000601:surgery
chemical_list: C497761:NOTCH1 protein, human; D051881:Receptor, Notch1