1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & Institute, Beijing, China.
2. Department of Chemistry, Durham University, Stockton Road, Durham DH1 3LE, U.K.
3. Department of Gastrointestinal Surgery, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China.
4. Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center laboratory, Peking University Cancer Hospital & Institute, Beijing, China
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 (P=0.001), TNM stage (P=0.023), lymph node metastasis (P=0.042) and peripheral blood CA19-9 level (P=0.049), while the transplantation rate of PDX models in MLC patients was significantly associated with tumor size (P=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.
Keywords: PDX, hepatocellular carcinoma, metastatic liver cancer, transplantation rate