Skip to main content
main-content

01.12.2018 | Research | Ausgabe 1/2018 Open Access

Journal of Translational Medicine 1/2018

Establishment and genomic characterizations of patient-derived esophageal squamous cell carcinoma xenograft models using biopsies for treatment optimization

Zeitschrift:
Journal of Translational Medicine > Ausgabe 1/2018
Autoren:
Jianling Zou, Ying Liu, Jingyuan Wang, Zhentao Liu, Zhihao Lu, Zuhua Chen, Zhongwu Li, Bin Dong, Wenwen Huang, Yanyan Li, Jing Gao, Lin Shen
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12967-018-1379-9) contains supplementary material, which is available to authorized users.
Jianling Zou and Ying Liu contributed equally to this work

Abstract

Background

Squamous cell carcinoma is the dominant type of esophageal cancer in China with many patients initially diagnosed at advanced stage. Patient-derived xenografts (PDX) models have been developed to be an important platform for preclinical research. This study aims to establish and characterize PDX models using biopsy tissue from advanced esophageal cancer patients to lay the foundation of preclinical application.

Methods

Fresh endoscopic biopsy tissues were harvested from patients with advanced esophageal cancer and implanted subcutaneously into NOD/SCID mice. Then, the PDXs were serially passaged for up to four generations. Transplantation was analyzed and genomic characteristics of xenografts were profiled using next-generation sequencing.

Results

Twenty-five PDX models were established (13.3%, 25/188). The latency period was 75.12 ± 19.87 days (50–120 days) for the first passage and it decreased with increasing passaging. Other than tumor stages, no differences were found between transplantations of xenografts and patient characteristics, irrespective of chemotherapy. Histopathological features and chemosensitivity of PDXs were in great accordance with primary patient tumors. Each PDX was assessed for molecular characteristics including copy number variations, somatic mutations, and signaling pathway abnormalities and these were similar to patient results.

Conclusions

Our PDX models were established from real time biopsies and molecularly profiled. They might be promising for drug development and individualized therapy.
Zusatzmaterial
Additional file 1: Table S1. The list of 483 cancer-associated genes. Table S2. Patient characteristics and transplantation rate. Table S3. Evaluation of histology and differentiation between primary patient tumor and the xenografts.
Additional file 2: Figure S1. Correlation between mRNA expression and CAN of FGF3 (a), FGF4 (b), and FGF19 (c) in esophageal PDX samples. The graph show mean values for two groups (CNV≥5 or CNV<5). The mRNA expression of the gene of interest was expressed in relation to that of β-actin, used as a housekeeping gene. Error bars represent ± S.E.M. (t-test).
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 1/2018

Journal of Translational Medicine 1/2018 Zur Ausgabe