A new biomarker panel for differential diagnosis of cholangiocarcinoma: Results from an exploratory analysis
Issued Date
2024-01-01
Resource Type
ISSN
03936155
eISSN
17246008
Scopus ID
2-s2.0-85189031251
Journal Title
International Journal of Biological Markers
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Journal of Biological Markers (2024)
Suggested Citation
Köhler B., Bes M., Chan H.L.Y., Esteban J.I., Piratvisuth T., Sukeepaisarnjaroen W., Tanwandee T., Thongsawat S., Mang A., Morgenstern D., Swiatek-de Lange M., Dayyani F. A new biomarker panel for differential diagnosis of cholangiocarcinoma: Results from an exploratory analysis. International Journal of Biological Markers (2024). doi:10.1177/03936155241235185 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/97878
Title
A new biomarker panel for differential diagnosis of cholangiocarcinoma: Results from an exploratory analysis
Author's Affiliation
Siriraj Hospital
Chinese University of Hong Kong, Faculty of Medicine
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
Roche Diagnostics GmbH
Faculty of Medicine, Khon Kaen University
Roche Molecular Systems
Centro de Transfusion y Banco de Tejidos
Hospital Universitari Vall d'Hebron
UCI School of Medicine
Prince of Songkla University
Universitätsklinikum Heidelberg
Chiang Mai University
Liver Cancer Center Heidelberg (LCCH)
Chinese University of Hong Kong, Faculty of Medicine
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
Roche Diagnostics GmbH
Faculty of Medicine, Khon Kaen University
Roche Molecular Systems
Centro de Transfusion y Banco de Tejidos
Hospital Universitari Vall d'Hebron
UCI School of Medicine
Prince of Songkla University
Universitätsklinikum Heidelberg
Chiang Mai University
Liver Cancer Center Heidelberg (LCCH)
Corresponding Author(s)
Other Contributor(s)
Abstract
Introduction: Diagnosis of cholangiocarcinoma (CCA) can be challenging due to unclear imaging criteria and difficulty obtaining adequate tissue biopsy. Although serum cancer antigen 19-9 and carcinoembryonic antigen have been proposed as potential diagnostic aids, their use remains limited by insufficient sensitivity and specificity. This exploratory analysis aimed to identify individual- and combinations of serum biomarkers to distinguish CCA from hepatocellular carcinoma (HCC) and chronic liver disease (CLD) controls using samples from a published study. Methods: This prospective, multicenter, case-control study included patients aged ≥18 years at high-risk of HCC. Serum and ethylene diamine tetraacetic acid-plasma samples were collected prior to any treatment and confirmed diagnosis of HCC or CCA. Fourteen biomarkers (measured by electrochemiluminescence immunoassays or enzyme-linked immunosorbent assays) were subjected to univariate analysis and 13 included in a multivariate analysis (per selected combinations and exhaustive search). Results: Overall, 55 CCA, 306 HCC, and 733 CLD control samples were analyzed. For distinguishing CCA from HCC, alpha-fetoprotein and matrix metalloproteinase-2 (MMP-2) showed the best individual performance (area under the curve (AUC) 86.6% and 84.4%, respectively); tissue inhibitor of metalloproteinase-1 (TIMP-1) was most able to distinguish CCA from CLD (AUC 94.5%) and from HCC + CLD (AUC 88.6%). The combination of MMP-2 and TIMP-1 was the best-performing two-marker panel, with AUC >90% for all comparisons. Conclusion: MMP-2 and TIMP-1 are promising biomarkers that could support differential diagnosis of CCA. Incorporating these assays into the diagnostic algorithm could provide additional diagnostic information in a non-invasive, rapid manner, and could supplement existing diagnostic methods.