Prognostic and predictive value of human equilibrative nucleoside transporter 1 (hENT1) in extrahepatic cholangiocarcinoma: a translational study

Frontiers in Pharmacology

Pharmacology

Hanneke W. M. Van Laarhoven¹  Jasmine Moustaquim²  Ali Belkouz²  Heinz-Josef Klümpen²  Elisa Giovannetti³  Gerrit K. J. Hooijer⁴  Joanne Verheij⁴  Eva Roos⁵  Joris I. Erdmann⁶  Geert Kazemier⁷  Lynn E. Nooijen⁸  Tessa Y. S. Le Large⁹  Lenka N. C. Boyd⁹  Robert Broos⁹  Jisce R. Puik⁹  Stephanie M. Fraga Rodrigues⁹  Mahsoem Ali⁹  Laura L. Meijer^1,10  Michal Heger^1,11 

[1] Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, Netherlands;Department of Medical Oncology, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands;Department of Medical Oncology, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands;Department of Medical Oncology, Lab of Medical Oncology, Amsterdam UMC, Location Vrije Universiteit, Amsterdam, Netherlands;Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, Netherlands;Cancer Pharmacology Lab, Associazione Italiana per La Ricerca Sul Cancro (AIRC) Start-Up Unit, Fondazione Pisana per La Scienza, Pisa, Italy;Department of Pathology, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands;Department of Pathology, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, Netherlands;Department of Surgery, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands;Department of Surgery, Amsterdam UMC, Location Vrije Universiteit, Amsterdam, Netherlands;Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, Netherlands;Department of Surgery, Amsterdam UMC, Location Vrije Universiteit, Amsterdam, Netherlands;Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, Netherlands;Department of Surgery, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands;Department of Surgery, Amsterdam UMC, Location Vrije Universiteit, Amsterdam, Netherlands;Department of Medical Oncology, Lab of Medical Oncology, Amsterdam UMC, Location Vrije Universiteit, Amsterdam, Netherlands;Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, Netherlands;Department of Surgery, Erasmus MC-University Medical Center, Rotterdam, Netherlands;Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiaxing, China;Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands;Erasmus Medical Center, Laboratory for Experimental Oncology, Department of Pathology, Rotterdam, Netherlands;

关键词: hENT1;    cholangiocarcinoma;    perihilar cholangiocarcinoma;    distal cholangiocarcinoma;    extrahepatic cholangiocarcinoma;    prognostic biomarker;    predictive biomarker;   

DOI  :  10.3389/fphar.2023.1274692

 received in 2023-08-09, accepted in 2023-09-27,  发布年份 2023

来源: Frontiers

【 摘 要 】

Introduction: Effective (neo) adjuvant chemotherapy for cholangiocarcinoma is lacking due to chemoresistance and the absence of predictive biomarkers. Human equilibrative nucleoside transporter 1 (hENT1) has been described as a potential prognostic and predictive biomarker. In this study, the potential of rabbit-derived (SP120) and murine-derived (10D7G2) antibodies to detect hENT1 expression was compared in tissue samples of patients with extrahepatic cholangiocarcinoma (ECC), and the predictive value of hENT1 was investigated in three ECC cell lines.Methods: Tissues of 71 chemonaïve patients with histological confirmation of ECC were selected and stained with SP120 or 10D7G2 to assess the inter-observer variability for both antibodies and the correlation with overall survival. Concomitantly, gemcitabine sensitivity after hENT1 knockdown was assessed in the ECC cell lines EGI-1, TFK-1, and SK-ChA-1 using sulforhodamine B assays.Results: Scoring immunohistochemistry for hENT1 expression with the use of SP120 antibody resulted in the highest interobserver agreement but did not show a prognostic role of hENT1. However, 10D7G2 showed a prognostic role for hENT1, and a potential predictive role for gemcitabine sensitivity in hENT1 in SK-ChA-1 and TFK-1 cells was found.Discussion: These findings prompt further studies for both preclinical validation of the role of hENT1 and histochemical standardization in cholangiocarcinoma patients treated with gemcitabine-based chemotherapy.

【 授权许可】

Unknown   
Copyright © 2023 Boyd, Nooijen, Ali, Puik, Moustaquim, Fraga Rodrigues, Broos, Belkouz, Meijer, Le Large, Erdmann, Hooijer, Heger, Van Laarhoven, Roos, Kazemier, Giovannetti, Verheij and Klümpen.