Jun Eunsung, Hong Seung-Mo, Yoo Hyun Ju, Kim Moon-Bo, Won Ji Sun, An Soyeon, Shim In Kyong, Chang Suhwan, Hoffman Robert M, Kim Song Cheol
Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea.
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, South Korea.
Oncotarget. 2017 Dec 21;9(8):7867-7881. doi: 10.18632/oncotarget.23567. eCollection 2018 Jan 30.
Tumors from 25 patients with pancreatic cancer were used to establish two patient-derived xenograft (PDX) models: orthotopic PDX (PDOX) and heterotopic (subcutaneous) PDX (PDHX). We compared gene expression by immunohistochemistry, single-nucleotide polymorphism (SNP), DNA methylation, and metabolite levels. The 4 cases, of the total of 13 in which simultaneous PDHX & PDOX models were established, were randomly selected. The molecular-genetic characteristics of the patient's tumor were well maintained in the two PDX models. SNP analysis demonstrated that both groups were more than 90% identical to the original patient's tumor, and there was little difference between the two models. DNA methylation of most genes was similar among the two models and the original patients tumor, but some gene sets were hypermethylated the in PDOX model and hypomethylated in the PDHX model. Most of the metabolites had a similar pattern to those of the original patient tumor in both PDX tumor models, but some metabolites were more prominent in the PDOX and PDHX models. This is the first simultaneous molecular-genetic and metabolite comparison of patient tumors and their tumors established in PDOX and PDHX models. The results indicate high fidelity of these critical properties of the patient tumors in the two models.
来自25例胰腺癌患者的肿瘤被用于建立两种患者来源的异种移植（PDX）模型：原位PDX（PDOX）和异位（皮下）PDX（PDHX）。我们通过免疫组织化学、单核苷酸多态性（SNP）、DNA甲基化和代谢物水平比较基因表达。在总共13例同时建立了PDHX和PDOX模型的病例中，随机选择了4例。患者肿瘤的分子遗传特征在两种PDX模型中得到了很好的保留。SNP分析表明，两组与原始患者肿瘤的相似度均超过90%，两种模型之间差异不大。两种模型与原始患者肿瘤中大多数基因的DNA甲基化相似，但一些基因集在PDOX模型中高甲基化，在PDHX模型中低甲基化。在两种PDX肿瘤模型中，大多数代谢物的模式与原始患者肿瘤相似，但一些代谢物在PDOX和PDHX模型中更为突出。这是首次对患者肿瘤及其在PDOX和PDHX模型中建立的肿瘤进行同时的分子遗传和代谢物比较。结果表明这两种模型中患者肿瘤的这些关键特性具有高保真度。
