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

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.

Identification of Prognostic Markers of Gynecologic Cancers Utilizing Patient-Derived Xenograft Mouse Models

“…According to previous reports, various factors influence the establishment of PDX, but more aggressive and poor prognostic types show a higher PDX success rate. These phenomena tend to be consistent regardless of tumor origin [21,31,32]. Based on these phenomena, the prognosis of patients can be predicted by comparing gene expression alterations between cancer tissues in PDX engraftment success and failure.…”

Establishment and evaluation of retroperitoneal liposarcoma patient-derived xenograft models: an ideal model for preclinical study

“…Our team also built a group of PDX models for pancreatic ductal adenocarcinoma (PDAC) and hepatocellular carcinoma (HCC) using similar methods 22 , 23 . In contrast to our findings in RLPS, no significant correlation was found between PDAC PDX engraftment rate and clinicopathological features or prognosis.…”

Protocol for chronic hepatitis B virus infection mouse model development by patient-derived orthotopic xenografts

“…Blood samples from animals will be collected under Isoflurane anesthesia by the facial vein puncture with a 20G needle. The size of subcutaneous neoplasm will be measured using a micrometer screw gauge, and its volume will be calculated by the formula: tumor volume = (length×width 2 )/2 [ 55 ]. When the tumors will be reached 0.4 to 0.6 cm in diameter, the tumor-bearing mice will be subjected to in vivo imaging studies.…”

“…Similar manipulations will be performed with the spleens of 4 mice in each group. The liver and spleen wounds will be closed with Surgicel ( Johnson & Johnson , USA) [ 55 , 60 , 61 ]. Muscle wounds will be sutured continuously with Vicryl W9113 4/0.…”