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

Yoon Young Choi, Jae Eun Lee, Hyunki Kim, Moon Hee Sim, Ka Kyung Kim, Gunho Lee, Hyoung Il Kim, Ji Yeong An, Woo Jin Hyung, Choong Bai Kim, Sung Hoon Noh, Sangwoo Kim, Jae Ho Cheong

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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.

Original languageEnglish
Article number22172
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 Mar 1

All Science Journal Classification (ASJC) codes

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    Choi, Y. Y., Lee, J. E., Kim, H., Sim, M. H., Kim, K. K., Lee, G., Kim, H. I., An, J. Y., Hyung, W. J., Kim, C. B., Noh, S. H., Kim, S., & Cheong, J. H. (2016). Establishment and characterisation of patient-derived xenografts as paraclinical models for gastric cancer. Scientific reports, 6, [22172]. https://doi.org/10.1038/srep22172