Establishment and characterization of patient-derived tumor xenograft using gastroscopic biopsies in gastric cancer.

Abstract

The patient-derived tumor xenograft (PDTX) model has become the most realistic model for preclinical studies. PDTX models of gastric cancer using surgical tissues are reported occasionally; however, the PDTX models using gastroscopic biopsies, which are best for evaluating new drugs, are unreported. In our study, a total of 185 fresh gastroscopic biopsies of gastric cancer were subcutaneously transplanted into NOD/SCID (Nonobese Diabetic/Severe Combined Immunodeficiency) mice. Sixty-three PDTX models were successfully established (34.1%, 63/185) and passaged to maintain tumors in vivo, and the mean latency period of xenografts was 65.86 6 32.84 days (11-160 days). Biopsies of prior chemotherapy had a higher transplantation rate (52.1%, 37/71) than biopsies after chemotherapy (21.9%, 25/114; P 5 0.000). No differences were found between the latency period of xenografts and characteristics of patients. The pathological and molecular features of PDTX as well as chemosensitivity were highly consistent with those of primary tumors of patients. The genetic characteristics were stable during passaging of PDTX models. In summary PDTX models using gastroscopic biopsies in gastric cancer were demonstrated for the first time, and the biological characteristics of the PDTX models were highly consistent with patients, which provided the best preclinical study platform for gastric cancer.T he percentage of advanced gastric cancer (AGC) in China is very high with poor prognosis and high mortality 1 . The comprehensive treatment based on fluorouracil containing chemotherapy is the main strategy for AGC. Although the addition of targeted drugs (trastuzumab, apatinib, and ramucirumab) [2][3][4] has improved the prognosis to some extent in recent years, the clinical outcome of AGC is not satisfactory due to the fewer therapeutic drugs and frequent drug resistance resulting from high heterogeneity and other mechanisms. As a consequence, developing new drugs and exploring the mechanisms of drug resistance are very urgent for AGC.Currently, the most commonly used models for developing new drugs are in vitro cell lines or in vivo animal models established by injection of cell lines 5,6 . With the rapid progression of scientific research, the above models are unable to meet the clinical needs. It is well known that almost all cell lines are subcultured many times in vitro and lose most features of patients 7,8 . Moreover, the microenvironment of in vitro cell lines is completely different from primary tumors of patients due to lack of tumor-associated stroma and blood supply, and so on 9 . A kind of ideal model is needed for the preclinical study.Patient-derived tumor xenograft (PDTX) models have become popular in the last several years with more advantages than cell line-based models [10][11][12] . Nowadays, most PDTX models are established by subcutaneously transplanting tumor tissues of patients into NOD/SCID (Nonobese Diabetic/Severe Combined Immunodeficiency) mice, and the biological characteristics of PDTX models are consistent w...