Bile carcinoembryonic cell adhesion molecule 6 (CEAM6) as a biomarker of malignant biliary stenoses |
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| Institution: | 1. Biomedical Proteomics Research Group, Department of Human Protein Sciences, Geneva University, Geneva CH-1211, Switzerland;2. Division of Gastroenterology and Hepatology, Geneva University Hospitals, Geneva CH-1211, Switzerland;3. Clinical Proteomics Laboratory, Department of Genetic and Laboratory Medicine, Geneva University Hospitals, Geneva CH-1211, Switzerland;4. Department of Gastroenterology, Erasme Hospital, Free University of Brussels, Brussels BE-1070, Belgium;1. Department of Medicine, Division of Hematology and Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America;2. Department of Physiology and Regenerative Medicine, Kindai University Faculty of Medicine, Osaka, Japan;3. Division of Infectious Diseases, Department of Clinical Microbiology, Umeå University, Sweden;4. Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM, United States of America;1. Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Duesseldorf, Germany;2. Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center, Duesseldorf, Germany;3. Institute of Experimental Genetics, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), Neuherberg, Germany;4. Center for Molecular Medicine Cologne, Cologne, Germany;5. Max Planck Institute for Biology of Ageing, Cologne, Germany;6. Multimedia Center, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany;7. Experimental Genetics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, Freising-Weihenstephan, Germany;8. Division of Endocrinology, Diabetology, Angiology, Nephrology, Pathobiochemistry and Clinical Chemistry, Department of Internal Medicine, University Tuebingen, Germany;9. Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum Muenchen at the University of Tuebingen, Tuebingen, Germany;10. Department of Endocrinology, Ghent University Hospital, Ghent, Belgium;11. German Center for Diabetes Research (DZD), Germany;1. Laboratory of Physiology I, School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Sagamihara, Kanagawa 252-5201, Japan;2. Miyagi Prefectural Meat Sanitation Inspection Station, 314 Imaizumi, Sakuraoka, Yoneyamacho, Tome City, Miyagi 987-0031, Japan;3. Piglet Co., Ltd., 1309-2 Komegome, Asahi City, Chiba 289-0516, Japan;4. Research Institute of Biosciences, School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Sagamihara, Kanagawa 252-5201, Japan;5. Laboratory of Anatomy I, School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Sagamihara, Kanagawa 252-5201, Japan;6. Laboratory of Physiology II, School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Sagamihara, Kanagawa 252-5201, Japan;7. Laboratory of Anatomy II, School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Sagamihara, Kanagawa 252-5201, Japan |
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| Abstract: | Differentiating malignant from nonmalignant biliary stenoses is challenging. This could be facilitated by the measurement of cancer biomarkers in bile. We aimed at (i) identifying new cancer biomarkers by comparative proteomic analysis of bile collected from patients with a malignant or benign biliary stenosis (exploratory phase) and (ii) verifying the accuracy of the newly identified potential biomarkers for discriminating malignant versus nonmalignant biliary stenoses in a larger group of patients (confirmation phase). Overall, 66 proteins were found overexpressed (ratio > 1.5) in at least one cancer condition using proteomic analysis and 7 proteins were increased in all malignant/nonmalignant disease comparisons. Preliminary screening by immunoblot highlighted carcinoembryonic cell adhesion molecule 6 (CEAM6), a cell surface protein overexpressed in many human cancers, as an interesting candidate biomarker. ELISA subsequently confirmed CEAM6 as a potential bile biomarker for distinguishing malignant from benign biliary stenoses with a receiver operating characteristic (ROC) area under the curve (AUC) of 0.92 (specificity 83%, sensitivity 93%, positive predictive value 93%, and negative predictive value 83%). No significant difference in serum CEAM6 level was found between malignant and nonmalignant samples. Combining bile CEAM6 and serum CA19-9 in a panel further improved diagnostic accuracy for malignant stenoses (AUC 0.96, specificity 83%, sensitivity 97%, positive predictive value 93%, and negative predictive value 91%). CEAM6 measurement in bile could be clinically useful to discriminate between malignant and nonmalignant causes of biliary stenosis. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge. |
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