• Barney Stephenson, Neil Shimwell, Elizabeth Humphreys, Douglas Ward, David Adams, Ashley Martin, and Simon Afford.
• NIHR Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK. Electronic address: barneys@doctors.org.uk.
• Lancet. 2015 Feb 26;385 Suppl 1:S94.

BackgroundCholangiocarcinoma has a high mortality and morbidity. Median survival is less than 6 months. Surgical resection is appropriate in certain circumstances. Because distal cholangiocarcinoma is difficult to distinguish from pancreatic cancers, patients might not receive optimum therapy. Proteomics is the study of complex cellular proteins using mass spectrometry. The aim of this study was to determine the constituent proteins on the cell surface of a model of cholangiocarcinoma.MethodsA sample preparation technique to enrich for cell surface proteins of the intrahepatic cholangiocarcinoma cell line CC-SW-1 was developed by modifying a NeutrAvidin-biotin system. After isolation, trypsin digestion, and purification, peptides were fractionated for tandem mass spectrometry before being analysed with the NCBInr database and the Mascot search algorithm. Results were confirmed by immunohistochemistry using a peroxidase detection technique on paraffin-embedded sections from resected specimens.FindingsPeptide enrichment was confirmed by electrophoresis. 862 proteins were consistently expressed between samples (n=3). 271 of these proteins were attributed only to the cell surface. They included proteins used clinically for staging disease (cytokeratin 19 [CK19]), identifying cancer stem cells (epithelial cell adhesion molecule [EpCAM], neural cell adhesion molecule [NCAM], epithelial growth factor receptor [EGFR]), and indicating potential for differentiation (Frozzled receptor, Notch pathway). Novel markers from the tumour necrosis factor (TNF) receptor superfamily were also identified. Immunohistochemistry confirmed these findings.InterpretationThe results from this surface proteomic profiling could help to identify novel therapeutic targets in cholangiocarcinoma. Further development of this technique could be translated to distinguish between distal cholangiocarcinoma and pancreatic cancers.FundingUK Medical Research Council.Copyright © 2015 Elsevier Ltd. All rights reserved.

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