Establishment of a Chinese library of patient-derived xenografts from gastrointestinal cancers.

Abstract

Background: Patient-derived xenografts (PDX) models have been regarded as an important tool for preclinical research. The aim of this study was to establish a Chinese PDX library from gastrointestinal cancers, especially esophageal squamous cell carcinoma (ESCC), esophagogastric junction adenocarcinoma (EGJAC), and gastric adenocarcinoma (GAC).

Methods: 1001 surgical tissues or endoscopic biopsy tissues of gastrointestinal cancers were subcutaneously implanted into NOD/SCID mice between January 2013 and August 2015. Engraftment rates, latency period of xenograft formation, patients' clinicopathological characteristics and survival associated with xenografts for ESCC, EGJAC and GAC were assessed.

Results: 208 PDX models were established (20.8%, 208/1001), among which 82 were from ESCC (21.2%, 82/386), 31 from EGJAC (16.9%, 31/183), and 29 from GAC (10.9%, 29/266). The average latency period of xenograft formation of ESCC, EGJAC, and GAC was 76.2, 90.5, and 85.2 days, respectively, for the first passage, and decreased to 52.5, 54.8, and 52.6 days, respectively for the second passage. For ESCC, gender, specimen type and differentiation were associated with engraftment; and for GAC, the factors associated with engraftment were age, specimen type, differentiation, and Lauren classification. The median follow-up of patients with ESCC, EGJAC and GAC was 46, 64 and 64 months, respectively. For GAC, the survival time of patients from whom the tumor tissues achieved successful engraftment was significantly shorter than that without xenograft formation.

Conclusions: We established a Chinese PDX library from gastrointestinal cancers, especially ESCC, a characteristic tumor type in China, providing a platform for drug development and individualized therapy.