Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & Institute, Beijing, China.
Department of Chemistry, Durham University, Stockton Road, Durham DH1 3LE, U.K.
Int J Med Sci. 2020 Oct 22;17(18):3073-3081. doi: 10.7150/ijms.46686. eCollection 2020.
Patient-derived xenograft (PDX) models are effective preclinical cancer models that reproduce the tumor microenvironment of the human body. The methods have been widely used for drug screening, biomarker development, co-clinical trials, and personalized medicine. However, the low success rate and the long tumorigenesis period have largely limited their usage. In the present studies, we compared the PDX establishment between hepatocellular cancer (HCC) and metastatic liver cancer (MLC), and identified the key factors affecting the transplantation rate of PDXs. Surgically resected tumor specimens obtained from patients were subcutaneously inoculated into immunodeficient mice to construct PDX models. The overall transplantation rate was 38.5% (20/52), with the HCC group (28.1%, 9/32) being lower than MLC group (56.2%, 9/16). In addition, HCC group took significantly longer latency period than MLC group to construct PDX models. Hematoxylin and eosin staining results showed that the histopathology of all generations in PDX models was similar to the original tumor in all three types of cancer. The transplantation rate of PDX models in HCC patients was significantly associated with blood type (=0.001), TNM stage (=0.023), lymph node metastasis (=0.042) and peripheral blood CA19-9 level (=0.049), while the transplantation rate of PDX models in MLC patients was significantly associated with tumor size (=0.034). This study demonstrates that PDX models can effectively reproduce the histological patterns of human tumors. The transplantation rate depends on the type of original tumor. Furthermore, it shows that the invasiveness of the original liver cancer affects the possibility of its growth in immunodeficient mice.
患者来源异种移植（PDX）模型是有效的临床前癌症模型，可重现人体的肿瘤微环境。这些方法已被广泛用于药物筛选、生物标志物开发、合作临床试验和个性化医疗。然而，低成功率和较长的致瘤期在很大程度上限制了它们的应用。在本研究中，我们比较了肝细胞癌（HCC）和转移性肝癌（MLC）的 PDX 建立情况，并确定了影响 PDX 移植率的关键因素。从患者手术切除的肿瘤标本中提取的肿瘤组织，通过皮下接种于免疫缺陷小鼠，构建 PDX 模型。总体移植率为 38.5%（20/52），其中 HCC 组（28.1%，9/32）低于 MLC 组（56.2%，9/16）。此外，HCC 组构建 PDX 模型的潜伏期明显长于 MLC 组。苏木精和伊红染色结果表明，PDX 模型中所有代际的组织病理学与三种癌症的原始肿瘤相似。HCC 患者 PDX 模型的移植率与血型（=0.001）、TNM 分期（=0.023）、淋巴结转移（=0.042）和外周血 CA19-9 水平（=0.049）显著相关，而 MLC 患者 PDX 模型的移植率与肿瘤大小（=0.034）显著相关。本研究表明，PDX 模型可以有效地复制人类肿瘤的组织学模式。移植率取决于原始肿瘤的类型。此外，它表明原发性肝癌的侵袭性影响其在免疫缺陷小鼠中生长的可能性。
