OBJECTIVES: @entity1125 ( @entity1125 ) is a fatal @entity5 originating from epithelial cells of the intra- and extra-hepatic biliary duct system and the gallbladder. Genes and pathways regulating stem and progenitor cells as well as cell-fate decisions are increasingly recognized in tumorigenesis. We evaluated the expression of @entity125 , @entity126 , and @entity1135 ( @entity1135 ), as well as the biliary cell-fate regulators @entity1935 ( @entity1935 ) and @entity5456 ( @entity5456 ), in @entity1125 for correlation with clinicopathological parameters. METHODS: Tissue microarrays including normal bile ducts and 111 BTCs consisting of 17 @entity1419 , 58 @entity201 , and 36 @entity1086 were analyzed using immunohistochemistry. RESULTS: Lack of cytoplasmic @entity1935 expression was associated with a higher @entity5 grade (P=0.010) and a significantly reduced overall survival (P=0.002; median 6 months vs. 24 months) in univariate survival analysis, whereas lack of nuclear @entity1935 expression was associated with a higher @entity5 stage (P=0.003). Notch pathway members showed high expression in @entity1125 . However, no correlation was found between cytoplasmic or nuclear @entity125 , @entity126 , and @entity1135 , as well as @entity5456 expression, and any of the clinicopathological parameters. In multivariate analysis, cytoplasmic @entity1935 expression was an independent prognostic factor for overall survival (P=0.031, relative risk=0.571). CONCLUSIONS: We show strong Notch pathway activation and identify @entity1935 as a prognostic marker in @entity1125 . These results substantiate diagnostic and therapeutic approaches targeting developmentally active genes and pathways.

Expression and clinicopathological significance of notch signaling and cell-fate genes in XXXX .

@entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer'] @entity1135 :: ('3280', 'Gene') :: ['HES1', 'hairy and enhancer of split 1'] @entity5456 :: ('6928', 'Gene') :: ['HNF1b', 'hepatocyte nuclear factor 1b'] @entity125 :: ('4851', 'Gene') :: ['Notch1'] @entity1935 :: ('6662', 'Gene') :: ['SOX9', 'SRY (sex determining region Y)-box 9'] @entity1419 :: ('MESH:C535533', 'Disease') :: ['intrahepatic cholangiocarcinomas'] @entity201 :: ('MESH:D018281', 'Disease') :: ['extrahepatic cholangiocarcinomas'] @entity1086 :: ('MESH:D005706', 'Disease') :: ['gallbladder carcinomas'] @entity1125 :: ('MESH:D001661', 'Disease') :: ['BTC', 'Biliary tract cancer'] @entity126 :: ('4853', 'Gene') :: ['Notch2']
@entity1125 :: (MESH:D001661,Disease) :: ['biliary tract cancer']
