Preliminary application of patient-derived tumor organoids in biliary tract cancers: analysis of 38 cases
10.3760/cma.j.cn112139-20250221-00088
- VernacularTitle:患者来源肿瘤类器官在胆道恶性肿瘤中的初步应用
- Author:
Yihang WANG
1
;
Xiaoxiao ZHANG
1
;
Yinghao GUO
1
;
Shuangda MIAO
1
;
Jiawei HU
1
;
Qi LI
1
;
Yanzhi PAN
1
;
Haoran DIAO
1
;
Yun JIN
1
;
Yuanquan YU
1
;
Jiangtao LI
1
Author Information
1. 浙江大学医学院附属第二医院肝胆胰外科，杭州 310009
- Publication Type:Journal Article
- Keywords:
Biliary Tract Cancers;
Patient-derived organoids;
Drug susceptibility testing;
Personal therapy
- From:
Chinese Journal of Surgery
2025;63(11):1044-1051
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore genomic features associated with gemcitabine sensitivity, patient-derived organoid models of biliary tract cancer (BTC) were established and characterized.Methods:This is an experimental study. The tissue specimens of BTC were collected from patients who underwent surgical resection at the Department of Hepatobiliary and Pancreatic Surgery,the Second Affiliated Hospital of Zhejiang University School of Medicine between January 2020 and December 2023. The tumor organoids were cultured in vitro and histologically characterized. Drug sensitivity testing was performed using gemcitabine,cisplatin,paclitaxel,fluorouracil,and lenvatinib etc. to evaluate cell viability. The correlation between the drug sensitivity of organoids and clinical therapeutic response was analyzed.Results:Thirty-eight patient-derived organoids (PDO) models were successfully established from 43 biliary tract malignancy patients with complete follow-up data,including gallbladder cancer PDO 14 cases,distal bile duct cancer PDO 16 cases,intrahepatic cholangiocarcinoma PDO 8 cases,achieving an overall success rate of 88.4%. Drug sensitivity testing (DST) was performed on the successfully generated PDO,with 35 models successfully completing DST experiments. The overall consistency rate between drug responses in PDOs and clinical survival outcomes in corresponding patients was 8/14. Transcriptomic analysis of gemcitabine-sensitive vs. gemcitabine-resistant PDO identified 71 differentially expressed genes in the resistant group,the significantly up-regulated genes including GLDC, LINC01595, IL-27, ANGPTL3, CYP7A1,and AKR1C1;the significantly down-regulated genes including P2RY2,LIPC,and ECHDC3. Conclusion:A biobank of patient-derived organoids of BTC has been established,which demonstrates its potential as preclinical models and tools for predicting chemotherapy responses for BTC patients.
