Development of the patient-derived xenograft model for gallbladder carcinoma and gene screening for tumor associated mutations
10.3760/cma.j.cn113884-20210316-00101
- VernacularTitle:胆囊癌人源性肿瘤异种移植模型的建立及肿瘤相关突变基因筛选
- Author:
Fengliang SONG
1
;
Kecheng ZHANG
;
Zhong CHEN
;
Baohua ZHANG
Author Information
1. 南通大学附属医院肝胆胰脾外科，江苏南通 226001
- Keywords:
Gallbladder neoplasms;
Patient-derived xenograft;
Whole exon sequencing;
Genetic mutations
- From:
Chinese Journal of Hepatobiliary Surgery
2021;27(10):748-752
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To establish a patient-derived xenograft (PDX) model of gallbladder carcinoma (GBC) and to screen mutated genes associated with GBC with the aim to provide an effective preclinical model with novel therapeutic targets for individualized patient treatment.Methods:The PDX model of GBC was established by transplantation of fresh GBC tissues from 10 patients into subcutaneous tissues of nude mice. In two of these mice, the PDX tumor tissues were stained with HE, Ki67 immunohistochemical staining and whole exome sequencing (WES). The biological characteristics of the PDX tumor tissues were compared with those of the primary donor tumors in histological structure and molecular pathology, and a high-throughput screening of tumor mutation genes was then carried out.Results:In this study, the success rate of the PDX model of GBC was 70% (7/10). The pathological and growth characteristics of PDX tumor tissues and donor tumors were basically similar. In the 2 modeled cases sequenced by WES, the same rates between the harmful mutant genes in the PDX model and primary donor tumor were 71.4% (15/21) and 65.2% (15/23), and the same genes accounted for 93.8% (15/16) and 71.4% (15/21) in the harmful mutant gene of the PDX model. The 22 mutated genes, including TP53, ABCC4 and AMPD1, were involved both in the two donor tumors, and the model tumor tissues. Ten genes including TP53 and ABCC4 were screened out and they might be closely related to development of GBC by bioinformatics analysis.Conclusions:The PDX model of GBC could effectively be used in patients with GBC in this preclinical study on individualized patient treatment. In addition, 10 mutated genes, including TP53 and ABCC4 and the like, may be used as new potential therapeutic targets for GBC.
