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Oncological and genetic factors impacting PDX model construction with NSG mice in pancreatic cancer
Author(s) -
Guo Shiwei,
Gao Suizhi,
Liu Rendong,
Shen Jing,
Shi Xiaohan,
Bai Sijia,
Wang Huan,
Zheng Kailian,
Shao Zhuo,
Liang Chuanyu,
Peng Siying,
Jin Gang
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201800617r
Subject(s) - pancreatic cancer , medicine , cancer , transplantation , cancer research , pancreatic tumor , adenocarcinoma , in vivo , pancreatic ductal adenocarcinoma , pathology , oncology , biology , microbiology and biotechnology
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 mm 3 were subcutaneously implanted into the NOD/Shi‐scid/IL‐2Rγnull (NSG) mice. Once the xenograft reached 300–500 mm 3 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. FASEB J. 33, 873–884 (2019). www.fasebj.org