Establishment and characterisation of patient-derived xenografts as paraclinical models for gastric cancer

Abstract

The patient-derived xenograft (PDX) model is emerging as a promising translational platform to duplicate the characteristics of tumours. However, few studies have reported detailed histological and genomic analyses for model fidelity and for factors affecting successful model establishment of gastric cancer. Here, we generated PDX tumours surgically-derived from 62 gastric cancer patients. Fifteen PDX models were successfully established (24.2%, 15/62) and passaged to maintain tumours in immune-compromised mice. Diffuse type and low tumour cell percentage were negatively correlated with success rates (p = 0.005 and p = 0.025, respectively), while reducing ex vivo and overall procedure times were positively correlated with success rates (p = 0.003 and p = 0.01, respectively). The histology and genetic characteristics of PDX tumour models were stable over subsequent passages. Lymphoma transformation occurred in five cases (33.3%, 5/15), and all were in the NOG mouse, with none in the nude mouse. Together, the present study identified Lauren classification, tumour cell percentages, and ex vivo times along with overall procedure times, as key determinants for successful PDX engraftment. Furthermore, genetic and histological characteristics were highly consistent between primary and PDX tumours, which provide realistic paraclinical models, enabling personalised development of treatment options for gastric cancer.

Patient-derived xenografts of gastrointestinal cancers are susceptible to rapid and delayed B-lymphoproliferation

“…A recent study hypothesizes that the development of B‐LPLs might be related to the host's degree of immunodeficiency since no lymphomas formed after xenotransplantations of primary gastric carcinomas into nude mice, while five EBV‐associated lymphomas developed in nine PDX in more efficiently immunocompromised NOD.Cg‐ Prkdc scid II2rg tm Sug /Jic (NOG) mice . Still, generalizability of these data is limited due to the relatively small sample size.…”

“…found only 1 lymphoma in 43 CRC PDX (2%) in NOD/SCID mice, which is significantly lower than 38.3% of CRC PDX developing B‐LPLs in our cohort of PDX in more severely immunocompromised NSG mice. Notably, B‐LPLs in PDX apparently occur across a broad range of solid tumor entities …”

Acquired Resistance to FGFR Inhibitor in Diffuse-Type Gastric Cancer through an AKT-Independent PKC-Mediated Phosphorylation of GSK3β

“…Establishing PDX models for DGC has posed a significant challenge for us and others in the field (25,26). To overcome the difficulty in obtaining primary tumors of sufficient tumor cellularity from DGC tissues, we collected peritoneal ascites fluid from DGC patients (Supplementary Table S1) and depleted GlyA þ red blood cells and CD45 þ hematopoietic cells.…”

GPR177 promotes gastric cancer proliferation by suppressing endoplasmic reticulum stress‐induced cell death

“…Inducing ER stress may be a promising gastric cancer treatment strategy in combination with strategies for decreasing GPR177 levels, regardless of the gastric cancer subtype . From a clinical perspective, using patient‐derived xenograft models and patient‐specific molecular information, we can stratify gastric cancer patients according to tumor ER stress resistance and predict therapeutic outcomes of ER stress inducer treatments …”