Proteomic Landscape of Cholangiocarcinomas Reveals 3 Different Subgroups According to their Localization and the Aspect of Non-Tumor Liver - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue PROTEOMICS - Clinical Applications Année : 2018

Proteomic Landscape of Cholangiocarcinomas Reveals 3 Different Subgroups According to their Localization and the Aspect of Non-Tumor Liver

Julie Le Faouder
  • Fonction : Auteur
Elia Gigante
  • Fonction : Auteur
Thibaut Léger
Aurélie Beaufrère
  • Fonction : Auteur
Olivier Soubrane
Jean Michel Camadro
Valérie Paradis

Résumé

PURPOSE: Cholangiocarcinomas (CC), tumors derived from epithelial biliary cells, define a heterogeneous entity based upon their anatomic localization (intra- versus extrahepatic) and, for those developing in the liver, depending on the aspect of non-tumor liver (normal versus cirrhosis). The aim of the study was to characterize the molecular heterogeneity of the different types of CC by a global proteomic approach. EXPERIMENTAL DESIGN: Thirty-three tumor samples from 17 intrahepatic CC (iCC) including 9 and 8 developed on normal (iCCN ) and cirrhotic liver (iCCC ), respectively; 5 hilar CC (CCH ), 5 CC developed in the pancreatic portion of the bile duct (CCP ) and 6 hepatocellular carcinoma (HCC), were submitted to label-free quantitative proteomic analysis. Differentially expressed proteins were further analyzed by immunohistochemistry in a validation set of 30 CC. RESULTS: In the overall series, 4590 proteins were quantified. Unsupervised analysis revealed two main clusters: cluster 1 contained most the iCCC while cluster 2 was divided in 2 subgroups, one containing most of the iCCN and the other regrouping CCH and CCP . Compared to iCCN , iCCC displayed upregulation of molecules involved in cell adhesion and motility and in angiogenesis. Epithelial markers associated with secretory pathway (mucins and AGR2) as well as fibroblast markers (S100A4) were overexpressed in CCH compared to iCCN . CONCLUSION AND CLINICAL RELEVANCE: This study demonstrated that among iCC, iCCC is a specific entity, suggesting a major impact of the underlying liver condition on the tumor biology, and confirmed that extrahepatic CCs, including CCP and CCH, define an homogeneous subgroup.
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Dates et versions

hal-01955914 , version 1 (14-12-2018)

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Julie Le Faouder, Elia Gigante, Thibaut Léger, Miguel Albuquerque, Aurélie Beaufrère, et al.. Proteomic Landscape of Cholangiocarcinomas Reveals 3 Different Subgroups According to their Localization and the Aspect of Non-Tumor Liver. PROTEOMICS - Clinical Applications, 2018, 25 (11), pp.1800128. ⟨10.1002/prca.201800128⟩. ⟨hal-01955914⟩
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