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Establishment and drug screening of patient-derived extrahepatic biliary tract carcinoma organoids

BACKGROUND: Patient-derived organoids (PDO) have been proposed as a novel in vitro method of drug screening for different types of cancer. However, to date, extrahepatic biliary tract carcinoma (eBTC) PDOs have not yet been fully established. METHODS: We collected six samples of gallbladder carcinom...

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Autores principales: Wang, Zhiwei, Guo, Yinghao, Jin, Yun, Zhang, Xiaoxiao, Geng, Hao, Xie, Guangyuan, Ye, Dan, Yu, Yuanquan, Liu, Daren, Zhou, Donger, Li, Baizhou, Luo, Yan, Peng, Shuyou, Li, Jiangtao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487492/
https://www.ncbi.nlm.nih.gov/pubmed/34600546
http://dx.doi.org/10.1186/s12935-021-02219-w
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author Wang, Zhiwei
Guo, Yinghao
Jin, Yun
Zhang, Xiaoxiao
Geng, Hao
Xie, Guangyuan
Ye, Dan
Yu, Yuanquan
Liu, Daren
Zhou, Donger
Li, Baizhou
Luo, Yan
Peng, Shuyou
Li, Jiangtao
author_facet Wang, Zhiwei
Guo, Yinghao
Jin, Yun
Zhang, Xiaoxiao
Geng, Hao
Xie, Guangyuan
Ye, Dan
Yu, Yuanquan
Liu, Daren
Zhou, Donger
Li, Baizhou
Luo, Yan
Peng, Shuyou
Li, Jiangtao
author_sort Wang, Zhiwei
collection PubMed
description BACKGROUND: Patient-derived organoids (PDO) have been proposed as a novel in vitro method of drug screening for different types of cancer. However, to date, extrahepatic biliary tract carcinoma (eBTC) PDOs have not yet been fully established. METHODS: We collected six samples of gallbladder carcinoma (GBC) and one sample of extrahepatic cholangiocarcinoma (eCCA) from seven patients to attempt to establish eBTC PDOs for drug screening. We successfully established five GBC and one eCCA PDOs. Histological staining was used to compare structural features between the original tissues and cancer PDOs. Whole exome sequencing (WES) was performed to analyze the genetic profiles of original tissues and cancer PDOs. Drug screening, including gemcitabine, 5-fluorouracil, cisplatin, paclitaxel, infigratinib, and ivosidenib, was measured and verified by clinical effects in certain cases. RESULTS: Different PDOs exhibited diverse growth rates during in vitro culture. Hematoxylin and eosin staining demonstrated that the structures of most cancer PDOs retained the original structures of adenocarcinoma. Immunohistological and periodic acid-schiff staining revealed that marker expression in cancer PDOs was similar to that of the original specimens. Genetic profiles from the four original specimens, as well as paired cancer PDOs, were analyzed using whole exome sequencing. Three of the four PDOs exhibited a high degree of similarity when compared to the original specimens, except for GBC2 PDO, which only had a concordance of 74% in the proportion of single nucleotide polymorphisms in the coding sequence. In general, gemcitabine was found to be the most efficient drug for eBTC treatment, as it showed moderate or significant inhibitory impact on cancer growth. Results from drug screening were confirmed to a certain extent by three clinical cases. CONCLUSIONS: Our study successfully established a series of eBTC PDOs, which contributed to the field of eBTC PDOs. Additional enhancements should be explored to improve the growth rate of PDOs and to preserve their immune microenvironment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-02219-w.
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spelling pubmed-84874922021-10-04 Establishment and drug screening of patient-derived extrahepatic biliary tract carcinoma organoids Wang, Zhiwei Guo, Yinghao Jin, Yun Zhang, Xiaoxiao Geng, Hao Xie, Guangyuan Ye, Dan Yu, Yuanquan Liu, Daren Zhou, Donger Li, Baizhou Luo, Yan Peng, Shuyou Li, Jiangtao Cancer Cell Int Primary Research BACKGROUND: Patient-derived organoids (PDO) have been proposed as a novel in vitro method of drug screening for different types of cancer. However, to date, extrahepatic biliary tract carcinoma (eBTC) PDOs have not yet been fully established. METHODS: We collected six samples of gallbladder carcinoma (GBC) and one sample of extrahepatic cholangiocarcinoma (eCCA) from seven patients to attempt to establish eBTC PDOs for drug screening. We successfully established five GBC and one eCCA PDOs. Histological staining was used to compare structural features between the original tissues and cancer PDOs. Whole exome sequencing (WES) was performed to analyze the genetic profiles of original tissues and cancer PDOs. Drug screening, including gemcitabine, 5-fluorouracil, cisplatin, paclitaxel, infigratinib, and ivosidenib, was measured and verified by clinical effects in certain cases. RESULTS: Different PDOs exhibited diverse growth rates during in vitro culture. Hematoxylin and eosin staining demonstrated that the structures of most cancer PDOs retained the original structures of adenocarcinoma. Immunohistological and periodic acid-schiff staining revealed that marker expression in cancer PDOs was similar to that of the original specimens. Genetic profiles from the four original specimens, as well as paired cancer PDOs, were analyzed using whole exome sequencing. Three of the four PDOs exhibited a high degree of similarity when compared to the original specimens, except for GBC2 PDO, which only had a concordance of 74% in the proportion of single nucleotide polymorphisms in the coding sequence. In general, gemcitabine was found to be the most efficient drug for eBTC treatment, as it showed moderate or significant inhibitory impact on cancer growth. Results from drug screening were confirmed to a certain extent by three clinical cases. CONCLUSIONS: Our study successfully established a series of eBTC PDOs, which contributed to the field of eBTC PDOs. Additional enhancements should be explored to improve the growth rate of PDOs and to preserve their immune microenvironment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-02219-w. BioMed Central 2021-10-02 /pmc/articles/PMC8487492/ /pubmed/34600546 http://dx.doi.org/10.1186/s12935-021-02219-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Primary Research
Wang, Zhiwei
Guo, Yinghao
Jin, Yun
Zhang, Xiaoxiao
Geng, Hao
Xie, Guangyuan
Ye, Dan
Yu, Yuanquan
Liu, Daren
Zhou, Donger
Li, Baizhou
Luo, Yan
Peng, Shuyou
Li, Jiangtao
Establishment and drug screening of patient-derived extrahepatic biliary tract carcinoma organoids
title Establishment and drug screening of patient-derived extrahepatic biliary tract carcinoma organoids
title_full Establishment and drug screening of patient-derived extrahepatic biliary tract carcinoma organoids
title_fullStr Establishment and drug screening of patient-derived extrahepatic biliary tract carcinoma organoids
title_full_unstemmed Establishment and drug screening of patient-derived extrahepatic biliary tract carcinoma organoids
title_short Establishment and drug screening of patient-derived extrahepatic biliary tract carcinoma organoids
title_sort establishment and drug screening of patient-derived extrahepatic biliary tract carcinoma organoids
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487492/
https://www.ncbi.nlm.nih.gov/pubmed/34600546
http://dx.doi.org/10.1186/s12935-021-02219-w
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