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Research ArticleExperimental Studies

Epithelial–Mesenchymal Transition Phenotype and Peritumoral Immune Cell Infiltration in Advanced Biliary Tract Cancer

CHUNG RYUL OH, HYUNG-DON KIM, YEON-MI RYU, SEONMIN LEE, DANBEE KIM, DA SOL LEE, JAE HO JEONG, HEUNG-MOON CHANG, BAEK-YEOL RYOO, KYU-PYO KIM, MIYEON KIM, SANG-YEOB KIM and CHANGHOON YOO
Anticancer Research February 2023, 43 (2) 645-652; DOI: https://doi.org/10.21873/anticanres.16201
CHUNG RYUL OH
1Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea;
2Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea;
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HYUNG-DON KIM
1Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea;
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YEON-MI RYU
3Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea;
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SEONMIN LEE
4Digestive Disease Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea;
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DANBEE KIM
1Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea;
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DA SOL LEE
1Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea;
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JAE HO JEONG
1Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea;
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HEUNG-MOON CHANG
1Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea;
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BAEK-YEOL RYOO
1Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea;
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KYU-PYO KIM
1Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea;
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MIYEON KIM
5Department of Medical Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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SANG-YEOB KIM
3Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea;
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  • For correspondence: sykim3yk@amc.seoul.kr
CHANGHOON YOO
1Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea;
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  • For correspondence: yooc@amc.seoul.kr
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Abstract

Background/Aim: This study evaluated the clinical implications of epithelial–mesenchymal transition (EMT) markers and peritumoral immune cell infiltration in patients with biliary tract cancer (BTC) treated with gemcitabine plus cisplatin (GemCis). Materials and Methods: Forty-five patients with advanced BTC who received GemCis were included as the study population. We conducted multiplex immunohistochemistry and examined EMT markers and their correlations with immune cell infiltrate at the invasive tumor margin. Study population was subdivided into two groups: twenty-four patients with overall survival (OS) less than 10 months (short-term survivor group, SS) and 21 with OS of 20 months or longer (long-term survivor group, LS). Results: The density of tumor cells expressing epithelial marker E-cadherin (E-cadherin+ CK+) at the invasive tumor margin tended to be higher in the LS group than that in the SS group (p=0.065). The density of tumor cells expressing mesenchymal marker vimentin (vimentin+ CK+) was significantly higher in the SS group than that in the LS group (p=0.021). The density of E-cadherin- vimentin+ tumor cells (E-cadherin- vimentin+ CK+) was also significantly higher in the SS group (p=0.020). The density of OX40 expressing cells was significantly higher in the SS group compared to that in the LS group (p=0.006). The density of vimentin-expressing tumor cells was positively correlated with FoxP3+ CD4+ regulatory T-cells (r=0.29, p=0.047) and OX40+ cells (r=0.48, p<0.001). Conclusion: EMT-related features were enriched in BTC patients with poor survival outcomes and associated with regulatory T-cell infiltration.

Key Words:
  • Epithelial-mesenchymal transition
  • biliary tract cancer
  • tumor microenvironment
  • regulatory T-cell
  • Received December 6, 2022.
  • Revision received December 13, 2022.
  • Accepted December 14, 2022.
  • Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Research: 43 (2)
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Epithelial–Mesenchymal Transition Phenotype and Peritumoral Immune Cell Infiltration in Advanced Biliary Tract Cancer
CHUNG RYUL OH, HYUNG-DON KIM, YEON-MI RYU, SEONMIN LEE, DANBEE KIM, DA SOL LEE, JAE HO JEONG, HEUNG-MOON CHANG, BAEK-YEOL RYOO, KYU-PYO KIM, MIYEON KIM, SANG-YEOB KIM, CHANGHOON YOO
Anticancer Research Feb 2023, 43 (2) 645-652; DOI: 10.21873/anticanres.16201

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Epithelial–Mesenchymal Transition Phenotype and Peritumoral Immune Cell Infiltration in Advanced Biliary Tract Cancer
CHUNG RYUL OH, HYUNG-DON KIM, YEON-MI RYU, SEONMIN LEE, DANBEE KIM, DA SOL LEE, JAE HO JEONG, HEUNG-MOON CHANG, BAEK-YEOL RYOO, KYU-PYO KIM, MIYEON KIM, SANG-YEOB KIM, CHANGHOON YOO
Anticancer Research Feb 2023, 43 (2) 645-652; DOI: 10.21873/anticanres.16201
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Keywords

  • epithelial-mesenchymal transition
  • Biliary tract cancer
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