Oncological and genetic factors impacting PDX model construction with NSG mice in pancreatic cancer.

Abstract

A patient-derived xenograft (PDX) approach, which relies on direct transplantation of tumor specimens into an immunocompromised animal, is a commonly used method for investigating tumor therapy predictions in vivo. This study evaluated influencing factors, including clinical, oncological, and genetic variables, for a pancreatic PDX model in mice. Tumor specimens were obtained from 121 patients with pancreatic ductal adenocarcinoma who underwent surgical resection at the Changhai Pancreatic Surgery Medical Center (Shanghai, China) between April 2016 and February 2017. Pancreatic cancer (PC) samples <3 mm3 were subcutaneously implanted into the NOD/Shi-scid/IL-2Rγnull (NSG) mice. Once the xenograft reached 300-500 mm3 or reached 180 d after cell inoculation, the tumor was excised. Part of the tumor was subsequently transplanted to next-generation mice, and another part was analyzed by using immunohistochemistry. Among the 121 patients with PC, tumor xenograft was successfully generated in 86 patients (71.1%). Primary tumor >3.5 cm in size was independently associated with xenograft formation rate. In addition, several enriched mutated genes within the VEGF pathway and higher microvessel density were found in the positive group (with xenograft) compared with the negative group (without xenograft). We concluded that tumor size and mutated VEGF pathway in PC are important factors affecting PDX model construction with NSG mice.-Guo, S., Gao, S., Liu, R., Shen, J., Shi, X., Bai, S., Wang, H., Zheng, K., Shao, Z., Liang, C., Peng, S., Jin, G. Oncological and genetic factors impacting PDX model construction with NSG mice in pancreatic cancer.