title: Epithelial cell adhesion molecule is a prognosis marker for intrahepatic cholangiocarcinoma.
abstract: BACKGROUND
  Recently, we identified a gene signature of intrahepatic cholangiocarcinoma (ICC) stroma and demonstrated its clinical relevance for prognosis. The most upregulated genes included epithelial cell adhesion molecule (EpCAM), a biomarker of cancer stem cells (CSC). We hypothesized that CSC biomarkers could predict recurrence of resected ICC.
  
  
  METHODS
  Both functional analysis of the stroma signature previously obtained and immunohistochemistry of 40 resected ICC were performed. The relationships between the expression of CSC markers and clinicopathologic factors including survival were assessed by univariate and multivariable analyzes.
  
  
  RESULTS
  Gene expression profile of the stroma of ICC highlighted embryonic stem cells signature. Immunohistochemistry on tissue microarray showed at a protein level the increased expression of CSC biomarkers in the stroma of ICC compared with nontumor fibrous liver tissue. The overexpression of EpCAM in the stroma of ICC is an independent risk factor for overall (hazard ratio = 2.6; 95% confidence interval, 1.3-5.1; P = 0.005) and disease-free survival (hazard ratio = 2.2; 95% confidence interval, 1.2-4.2; P = 0.012). In addition, the overexpression of EpCAM in nontumor fibrous liver tissue is closely correlated with a worst disease-free survival (P = 0.035).
  
  
  CONCLUSIONS
  Our findings provide new arguments for a potential role of CSC on ICC progression supporting the idea that targeting CSC biomarkers might represent a promise personalized treatment.
authors.affiliation: Liver Metabolisms and Cancer, INSERM UMR991, Rennes, France; Université de Rennes 1, Rennes, France; Service de Chirurgie Hépatobiliaire et Digestive, CHU Rennes, Rennes, France. Electronic address: laurent.sulpice@chu-rennes.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Sulpice
authors.affiliation: Université de Rennes 1, Rennes, France; Service de Chirurgie Hépatobiliaire et Digestive, CHU Rennes, Rennes, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Rayar
authors.affiliation: Liver Metabolisms and Cancer, INSERM UMR991, Rennes, France; Université de Rennes 1, Rennes, France; Service d'Anatomie et Cytologie Pathologiques, CHU Rennes, Rennes, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Turlin
authors.affiliation: Liver Metabolisms and Cancer, INSERM UMR991, Rennes, France; Université de Rennes 1, Rennes, France; Centre Régional de Lutte contre le Cancer, Rennes, France.
authors.forename: Eveline
authors.initials: E
authors.lastname: Boucher
authors.affiliation: Liver Metabolisms and Cancer, INSERM UMR991, Rennes, France; Université de Rennes 1, Rennes, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Bellaud
authors.affiliation: Liver Metabolisms and Cancer, INSERM UMR991, Rennes, France; Université de Rennes 1, Rennes, France.
authors.forename: Mireille
authors.initials: M
authors.lastname: Desille
authors.affiliation: Université de Rennes 1, Rennes, France; Service de Chirurgie Hépatobiliaire et Digestive, CHU Rennes, Rennes, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Meunier
authors.affiliation: Liver Metabolisms and Cancer, INSERM UMR991, Rennes, France; Université de Rennes 1, Rennes, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Clément
authors.affiliation: Liver Metabolisms and Cancer, INSERM UMR991, Rennes, France; Université de Rennes 1, Rennes, France; Service de Chirurgie Hépatobiliaire et Digestive, CHU Rennes, Rennes, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Boudjema
authors.affiliation: Liver Metabolisms and Cancer, INSERM UMR991, Rennes, France; Université de Rennes 1, Rennes, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Coulouarn
mesh_terms: D000071916:AC133 Antigen; D000368:Aged; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000601:surgery; D001653:Bile Ducts, Intrahepatic / Q000601:surgery; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000401:mortality* / Q000601:surgery; D000071858:Epithelial Cell Adhesion Molecule; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D059467:Transcriptome
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D010455:Peptides
keywords: Biomarkers; Intrahepatic cholangiocarcinoma; Prognosis