TY - JOUR
T1 - Prognostic and predictive value of human equilibrative nucleoside transporter 1 (hENT1) in extrahepatic cholangiocarcinoma
T2 - a translational study
AU - Boyd, Lenka N. C.
AU - Nooijen, Lynn E.
AU - Ali, Mahsoem
AU - Puik, Jisce R.
AU - Moustaquim, Jasmine
AU - Fraga Rodrigues, Stephanie M.
AU - Broos, Robert
AU - Belkouz, Ali
AU - Meijer, Laura L.
AU - le Large, Tessa Y. S.
AU - Erdmann, Joris I.
AU - Hooijer, Gerrit K. J.
AU - Heger, Michal
AU - van Laarhoven, Hanneke W. M.
AU - Roos, Eva
AU - Kazemier, Geert
AU - Giovannetti, Elisa
AU - Verheij, Joanne
AU - Klümpen, Heinz-Josef
N1 - Funding Information: The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by KWF Dutch Cancer Society, grant number 11957 (EG), Associazione Italiana per la Ricerca sul Cancro AIRC/IG-grant number IG-24444 (EG) and by the Bennink Foundation (EG, GK). Publisher Copyright: 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.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - cholangiocarcinoma
KW - distal cholangiocarcinoma
KW - extrahepatic cholangiocarcinoma
KW - hENT1
KW - perihilar cholangiocarcinoma
KW - predictive biomarker
KW - prognostic biomarker
UR - http://www.scopus.com/inward/record.url?scp=85175625071&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fphar.2023.1274692
DO - https://doi.org/10.3389/fphar.2023.1274692
M3 - Article
C2 - 37920204
SN - 1663-9812
VL - 14
SP - 1274692
JO - Frontiers in pharmacology
JF - Frontiers in pharmacology
M1 - 1274692
ER -