title: Tumoral heterogeneity of hepatic cholangiocarcinomas revealed by MALDI imaging mass spectrometry.
abstract: Cholangiocarcinoma (CC) is the second most common primary malignancy of the liver. Although all CC derive from biliary epithelial cells, two main subtypes, hilar (H), and peripheral (P) CC are described. The objective of the study was to compare, using MALDI imaging mass spectrometry (MALDI IMS), in situ proteomic profiles of H- and P-CC in order to assess whether these subtypes may express different markers and to describe their respective localizations. Twenty-seven CC (16 P-CC and 11 H-CC) were subjected to MALDI IMS. Proteomic data were submitted to a dedicated cross-classification comparative design, enabling comparison of the entire generated spectra. Immunohistochemistry was performed for validation. Comparative analysis yielded a list of 19 differential protein peaks for the two subtypes, 14 of which were overexpressed in H-CC and five in P-CC. Among H-CC protein markers, most discriminant were human neutrophil peptides 1-3 that were expressed mainly by tumor cells and S100 proteins (A6 and A11) that were restricted to the stromal area. In P-CC, thymosin β4 was diffusely overexpressed. These results highlight the potential of MALDI IMS to discover new relevant biomarkers of CC and to characterize the heterogeneity of the two different subtypes.
authors.affiliation: Claude Bernard Institute, Paris-Diderot University, Paris, France; INSERM U773, Biomedical Research Center, Paris-Diderot University, Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Le Faouder
authors.forename: Samira
authors.initials: S
authors.lastname: Laouirem
authors.forename: Theodore
authors.initials: T
authors.lastname: Alexandrov
authors.forename: Soundes
authors.initials: S
authors.lastname: Ben-Harzallah
authors.forename: Thibaut
authors.initials: T
authors.lastname: Léger
authors.forename: Miguel
authors.initials: M
authors.lastname: Albuquerque
authors.forename: Pierre
authors.initials: P
authors.lastname: Bedossa
authors.forename: Valérie
authors.initials: V
authors.lastname: Paradis
mesh_terms: D001650:Bile Duct Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D018281:Cholangiocarcinoma / Q000145:classification / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D018740:Genetic Heterogeneity; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D040901:Proteomics; D009418:S100 Proteins / Q000096:biosynthesis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D009363:Neoplasm Proteins; D009418:S100 Proteins
keywords: Biomarker; Biomedicine; Cholangiocarcinoma; MALDI imaging mass spectrometry