Proteomic profiling of cholangiocarcinoma: Diagnostic potential of SELDI-TOF MS in malignant bile duct stricture

Authors

  • Christopher J. Scarlett,

    1. Department of Surgery, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales, Australia
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    • Christopher J. Scarlett and Alex J. Saxby contributed equally to this study.

    • Scarlett is the recipient of a University of Sydney Postgraduate Award and is a Cancer Institute NSW Scholar.

  • Alex J. Saxby,

    1. Department of Surgery, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales, Australia
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    • Christopher J. Scarlett and Alex J. Saxby contributed equally to this study.

  • AiQun Nielsen,

    1. Department of Surgery, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales, Australia
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  • Cameron Bell,

    1. Department of Gastroenterology, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales, Australia
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  • Jaswinder S. Samra,

    1. Department of Surgery, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales, Australia
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  • Thomas Hugh,

    1. Department of Surgery, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales, Australia
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  • Robert C. Baxter,

    1. Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales, Australia
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    • Potential conflict of interest: Dr. Baxter advises Tissue Therapies Pty Limited. Dr. Smith is chairman of, and received funding from, CanSur Pty Limited. He is also chairman of Mictocatheters Pty Limited.

  • Ross C. Smith

    Corresponding author
    1. Department of Surgery, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales, Australia
    • University of Sydney, Department of Surgery, Royal North Shore Hospital, St Leonards, NSW, 2065, Australia
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    • Potential conflict of interest: Dr. Baxter advises Tissue Therapies Pty Limited. Dr. Smith is chairman of, and received funding from, CanSur Pty Limited. He is also chairman of Mictocatheters Pty Limited.

    • fax: (61) 2-9437-3522


Abstract

Proteomic techniques promise to improve the diagnosis of cholangiocarcinoma (CC) in both tissue and serum as histological diagnosis and existing serum markers exhibit poor sensitivities. We explored the use of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) to identify potential protein biomarkers of CC. Twenty-two resected CC samples were compared with adjacent noninvolved bile duct tissue. Serum from patients with CC (n = 20) was compared with patients with benign disease (n = 20), and healthy volunteers (n = 25). Samples were analyzed on hydrophobic protein chips via SELDI-TOF MS, and classification models were developed using logistic regression and cross-validation analysis. Univariate analysis revealed 14 individual peaks differentially expressed between CC and bile duct tissue, 4 peaks between CC and benign disease, and 12 peaks between CC and sera of healthy volunteers. The 4,462 mass-to-charge serum peak had superior discriminatory ability to carbohydrate antigen 19.9 (CA19.9) and carcinoembryonic antigen (CEA) (P = .004; receiver operating characteristic [ROC] area under the curve [AUC] = 0.76, 0.73, and 0.70, respectively). The training models developed panels of peaks that distinguished CC from bile duct tissue (92.5% sensitivity, 92.3% specificity; ROC AUC = 0.96), CC from benign serum (65.0% sensitivity, 70.0% specificity; ROC AUC = 0.83), and CC from sera of healthy volunteers (75.0% sensitivity, 100% specificity; ROC AUC = 0.92). Serum results were further improved with the inclusion of CA19.9 and CEA (ROC AUC = 0.86 and 0.99 for CC vs benign and healthy volunteer serum, respectively). In conclusion, biomarker panels are capable of distinguishing CC from nonmalignant tissue; serum markers have important diagnostic implications for unknown bile duct stricture. (HEPATOLOGY 2006;44:658–666.)

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