Tumoral heterogeneity of hepatic cholangiocarcinomas revealed by MALDI imaging mass spectrometry

Authors

  • Julie Le Faouder,

    Corresponding author
    1. Claude Bernard Institute, Paris-Diderot University, Paris, France
    2. INSERM U773, Biomedical Research Center, Paris-Diderot University, Paris, France
    • Correspondence: Dr. Julie Le Faouder, INSERM U773, Hôpital Beaujon, 100 Boulevard du Général Leclerc, 92110 Clichy, France

      E-mail: julie.lefaouder@inserm.fr

      Fax: +33-1-47-30-17-11

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  • Samira Laouirem,

    1. INSERM U773, Biomedical Research Center, Paris-Diderot University, Paris, France
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  • Theodore Alexandrov,

    1. Center for Industrial Mathematics, University of Bremen, Bremen, Germany
    2. Steinbeis Innovation Center SCiLS Research, Bremen, Germany
    3. SCiLS GmbH, Bremen, Germany
    4. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA
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  • Soundes Ben-Harzallah,

    1. INSERM U773, Biomedical Research Center, Paris-Diderot University, Paris, France
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  • Thibaut Léger,

    1. Mass Spectrometry Facility, Jacques Monod Institute, UMR7592-CNRS, University Paris-Diderot, Paris, France
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  • Miguel Albuquerque,

    1. Pathology Department, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France
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  • Pierre Bedossa,

    1. INSERM U773, Biomedical Research Center, Paris-Diderot University, Paris, France
    2. Pathology Department, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France
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  • Valérie Paradis

    1. INSERM U773, Biomedical Research Center, Paris-Diderot University, Paris, France
    2. Pathology Department, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France
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  • Colour Online: See the article online to view Figs. 1–3 in colour.

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.

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