Comprehensive comparison of patient-derived xenograft models in Hepatocellular Carcinoma and metastatic Liver Cancer

Xu, Wei; Zhao, Zheng-Yun; An, Qi-Ming; Dong, Bin; Lv, Ang; Li, Cheng-peng; Guan, Xiao-Ya; Tian, Xiu-Yun; Wu, Jian-Hui; Hao, Chun-Yi

Abstract

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.

Citation

Xu, W., Zhao, Z.-Y., An, Q.-M., Dong, B., Lv, A., Li, C.-P., Guan, X.-Y., Tian, X.-Y., Wu, J.-H., & Hao, C.-Y. (2020). Comprehensive comparison of patient-derived xenograft models in Hepatocellular Carcinoma and metastatic Liver Cancer. International Journal of Medical Sciences, 17(18), 3073-3081. https://doi.org/10.7150/ijms.46686

• Journal Article Type: Article
• Acceptance Date: Oct 7, 2020
• Publication Date: 2020
• Deposit Date: Nov 18, 2020
• Publicly Available Date: Nov 18, 2020
• Journal: International Journal of Medical Sciences
• Publisher: Ivyspring International Publisher
• Peer Reviewed: Peer Reviewed
• Volume: 17
• Issue: 18
• Pages: 3073-3081
• DOI: https://doi.org/10.7150/ijms.46686
• Public URL: https://durham-repository.worktribe.com/output/1256964