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

Yan Zhu,Na Li,Jianling Zou,Yanyan Li,Zhongwu Li,Jian Wu,Lai Wang,Tiantian Tian,Zhiyu Tang,Jing Gao,Lin Shen,Yilin Li,Bin Dong

doi:10.1038/srep08542

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 ± 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 = 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.

Highlights

The patient-derived tumor xenograft (PDTX) model has become the most realistic model for preclinical studies
PDTX models from various tumors have been established, such as colorectal cancer[17,18], breast cancer[15,19], nonsmall cell lung carcinoma[9,20], and renal cell carcinoma[21]
PDTX models from various tumors have been established, including gastric cancer[22,23,25,26], which was mostly derived from surgical tumor tissues

Summary

Introduction

The patient-derived tumor xenograft (PDTX) model has become the most realistic model for preclinical studies. 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. 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 with primary tumors of patients[13,14,15,16]. PDTX models of gastric cancer using surgical tissues are reported occasionally[22,23,24]; patients with AGC are the most suitable population to evaluate the efficacy of new drugs, and the major method to acquire tumor samples for AGC is gastroscopic biopsy, especially for paired samples before and after chemotherapy

Methods

Results

Conclusion