A new biomarker panel for differential diagnosis of cholangiocarcinoma: Results from an exploratory analysis
- PMID: 38549363
- DOI: 10.1177/03936155241235185
A new biomarker panel for differential diagnosis of cholangiocarcinoma: Results from an exploratory analysis
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.
Keywords: Cholangiocarcinoma; HCC; biomarkers; diagnosis; liquid biopsy.
Conflict of interest statement
Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: BK reports a non-related research grant with AbbVie, support for a clinical trial from Gilead Sciences, speaker's bureau participation for Servier, Takeda, and Pierre Fabre. HL-YC reports consultancy fees from Aligos Therapeutics Arbutus Biopharma, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceutica, Hepion, Roche, Vir Biotechnology, Vaccitech, and Viron Therapeutics and speaker's bureau participation for Gilead Sciences, Mylan, and Roche Diagnostics. TP reports speaker's bureau participation for Bristol-Myers Squibb, Gilead Science, Bayer, Abbott, and Eisai, plus MSD and research grant/contracts from Gilead Science, Roche Diagnostics, Janssen, FibroGen, and Vir Biotechnology. AM, and MSdL are employees of Roche Diagnostics and hold stock/stock options in F. Hoffman-La Roche Ltd. DM was an employee of Roche Diagnostics and held stock/stock options in F. Hoffman-La Roche Ltd at the time of analysis. MSdL has a patent for a new binding agent and assay for PIVKA-II pending, and a pending patent application on the TIMP-1/MMP-2 panel. FD is a consultant for Genentech/Roche, Array BioPharma, Exelixis, Eisai, QED Therapeutics, and Signatera. JIE, MB, ST, TT, and WS have nothing to disclose.
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