Hu H M, Zhang W L, Huang D S, Li R, Gu H L, Li J, Gao Y N
Department of Pediatrics, Beijing Tongren Hospital, Capital Medical University, Beijing 100176, China.
Department of Pathology, Beijing Tongren Hospital, Capital Medical University, Beijing 100176, China.
Zhonghua Gan Zang Bing Za Zhi. 2023 Oct 20;31(10):1075-1080. doi: 10.3760/cma.j.cn501113-20220218-00075.
To establish a patient-derived xenograft (PDX) humanized mouse model for hepatoblastoma in children. In addition, compare the biological consistency between successfully modeled PDX tumors and primary tumors in children while comparing and analyzing the influence of PDX model modeling success as a key factor. A PDX tumor model was constructed from fresh tumor tissue samples from 39 children with hepatoblastoma. The tumor growth time and volume size were recorded in detail. Simultaneously, 39 children's data were collected for experimental and clinical analysis. The difference in tumorigenesis rate between different parameters was analyzed by (2) test (categorical variable). Continuous variables with a normal distribution were compared using the t-test. After cell passage and pathological diagnosis, 21 cases of hepatoblastoma PDX models were successfully constructed, with a success rate of 53.8% (21/39). Tumor samples from each generation of successfully modeled PDX models had pathology results that were consistent with those of the corresponding primary tumors. The analysis of the key factors affecting the tumor formation rate of PDX revealed that the metastasis rate was more successful in primary tumors than in liver in situ tumors (7/8 vs. 14/31, = 0.049). However, there was no significant difference between tumor formation rates and pathological subtypes. According to the PDX tumor formation group comparison between the primary tumor and the metastatic tumor, there was no statistically significant difference between the two groups in terms of tumor formation time and tumor volume. Hematoxylin-eosin staining in hepatoblastoma's PDX mouse was consistent with the primary tumor. Immunohistochemistry positivity rates of four proteins, namely hepatocyte antigen (Hepatocyte), phosphatidylinositol glycan 3, β-catenin, and alpha-fetoprotein, in primary tumor tissues and PDX mouse models were 100% vs. 100%, 100% vs. 95.24%, 100% vs. 100%, and 95.24% vs. 85.71%, respectively. A PDX mouse model for hepatoblastoma has been successfully established in children. The tumor formation rate is high, with metastatic tumors having a higher tumor formation rate than primary tumors and transplanted tumors retaining the biological characteristics of primary tumors.
建立儿童肝母细胞瘤患者来源的异种移植（PDX）人源化小鼠模型。此外，比较成功建模的PDX肿瘤与儿童原发性肿瘤之间的生物学一致性，同时比较和分析PDX模型建模成功作为关键因素的影响。从39例儿童肝母细胞瘤的新鲜肿瘤组织样本构建PDX肿瘤模型。详细记录肿瘤生长时间和体积大小。同时，收集39例儿童的数据进行实验和临床分析。采用（2）检验（分类变量）分析不同参数之间肿瘤发生率的差异。使用t检验比较正态分布的连续变量。经过细胞传代和病理诊断，成功构建21例肝母细胞瘤PDX模型，成功率为53.8%（21/39）。每一代成功建模的PDX模型的肿瘤样本病理结果与相应原发性肿瘤一致。对影响PDX肿瘤形成率的关键因素分析显示，原发性肿瘤转移率比原位肝肿瘤更成功（7/8 vs. 14/31， = 0.049）。然而，肿瘤形成率与病理亚型之间无显著差异。根据原发性肿瘤与转移性肿瘤的PDX肿瘤形成组比较，两组在肿瘤形成时间和肿瘤体积方面无统计学显著差异。肝母细胞瘤PDX小鼠的苏木精-伊红染色与原发性肿瘤一致。原发性肿瘤组织和PDX小鼠模型中四种蛋白，即肝细胞抗原（Hepatocyte）、磷脂酰肌醇聚糖3、β-连环蛋白和甲胎蛋白的免疫组化阳性率分别为100% vs. 100%、100% vs. 95.24%、100% vs. 100%和95.24% vs. 85.71%。已成功建立儿童肝母细胞瘤的PDX小鼠模型。肿瘤形成率高，转移性肿瘤的肿瘤形成率高于原发性肿瘤，移植肿瘤保留原发性肿瘤的生物学特性。
