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Synergistic effects of extracellular vesicle phenotyping and AFP in hepatobiliary cancer differentiation.

Liver international : official journal of the International Association for the Study of the Liver

Authors: Sabine K Urban, Hanna Sänger, Marcin Krawczyk, Henrike Julich-Haertel, Arnulf Willms, Joanna Ligocka, Mikel Azkargorta, Tudor Mocan, Christoph Kahlert, Beata Kruk, Krzysztof Jankowski, Waldemar Patkowski, Marek Krawczyk, Krzysztof Zieniewicz, Wacław Hołówko, Łukasz Krupa, Mateusz Rzucidło, Krzysztof Gutkowski, Wojciech Wystrychowski, Robert Król, Joanna Raszeja-Wyszomirska, Artur Słomka, Robert Schwab, Aliona Wöhler, Maria A Gonzalez-Carmona, Sebastian Gehlert, Zeno Sparchez, Jesus M Banales, Christian P Strassburg, Frank Lammert, Piotr Milkiewicz, Miroslaw Kornek

BACKGROUND: Biliary cancer, comprising cholangio- and gallbladder carcinomas, is associated with high mortality due to asymptomatic disease onset and resulting late diagnosis. Currently, no robust diagnostic biomarker is clinically available. Therefore, we explored the feasibility of extracellular vesicles (EVs) as a liquid biopsy tool for biliary cancer screening and hepatobiliary cancer differentiation.

METHODS: Serum EVs of biliary cancer, hepatocellular carcinoma, colorectal cancer and non-small cell lung cancer patients, as well as from healthy individuals, were isolated by sequential two-step centrifugation and presence of indicated EVs was evaluated by fluorescence activated cell sorting (FACS) analysis.

RESULTS: Two directly tumour-related antigen combinations (AnnV CD44v6 and AnnV CD44v6 CD133 ) and two combinations related to progenitor cells from the tumour microenvironment (AnnV CD133 gp38 and AnnV EpCAM CD133 gp38 ) were associated with good diagnostic performances that could potentially be used for clinical assessment of biliary cancer and differentiation from other cancer entities. With 91% sensitivity and 69% specificity AnnV CD44v6 EVs showed the most promising results for differentiating biliary cancers from HCC. Moreover using a combined approach of EV levels of the four populations with serum AFP values, we obtained a perfect separation of biliary cancer and HCC with sensitivity, specificity, positive and negative predictive value all reaching 100% respectively.

CONCLUSIONS: EV phenotyping, especially if combined with serum AFP, represents a minimally invasive, accurate liquid biopsy tool that could improve cancer screening and differential diagnosis of hepatobiliary malignancies.

© 2020 The Authors. Liver International published by John Wiley & Sons Ltd.

PMID: 32614460

Participating cluster members