An improved method to build lung cancer PDX models by surgical resection samples and its association with B7-H3 expression

Yuxuan Wang, Biao Zhang, Haitao Huang, Tingjing Wang


Background: Patient-derived xenograft (PDX) models are biologically stable and can accurately reflect the primary tumor in histopathology and genetic expression in many cancers. In lung cancer, the models’ engraftment rate by endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) and computed tomography (CT)-guided biopsy is exceptionally low, and this limits the development of PDX models in lung cancer research. In this study, we aimed to improve the traditional method, and explore the feasibility and convenience of establishing lung cancer PDX models using the samples directly from surgical resection. We also endeavored to explore the correlation between PDX formation and primary tumor B7-H3 protein expression.
Methods: From September 2017 to July 2018, 24 patients were enrolled in this study. The pathological diagnoses were as follows: 15 adenocarcinomas, 7 squamous cell carcinomas, 1 large cell carcinoma, and 1 small cell carcinoma. The tumor tissues were cut into sizes of 2×2×2 mm3/fragment and inoculated subcutaneously into immunodeficiency mice with a trocar needle. The engrafted tumors were passaged at least 3 generations, and B7-H3 IHC staining was performed on primary tumors. To explore the correlation between PDX formation and B7-H3 protein expression, we also performed H&E staining to evaluate whether the established PDX models could retain the histological features of the primary tumor.
Results: Xenograft formation success was achieved in 19 out of 24 cases (79.2%). The time between implantation to tumor formation was an average of 81.5 days (27–154 days) in P1, an average of 44.4 days (14–122 days) in P2, and an average of 26.9 days (12–75 days) in P3. The diameter of the tumor was associated with tumor engraftment: the longer the diameter, the easier engraftment formation was (P=0.0342). The data also suggests that lung cancers with B7-H3 expression greatly induced PDX formation (P=0.0375). The histological characters of each passage resembled the primary tumors.
Conclusions: This study shows that the samples from carefully selected lung cancer by surgical resection can be used for the establishment of PDX models with a high success rate; this improved method is closer to actual clinical work. Compared with the same kind of research, the success rate of the xenograft indicates significant improvement, so this improved method is suitable for promotion and application. The results of H&E staining showed that the histological characters of each passage resembled the primary tumors. Furthermore, the diameter of the tumor was associated with tumor engraftment, and higher B7-H3 expression demonstrated a statistically significant difference compared with the PDX model formation.