title: 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.
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.|Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Yoon Young
authors.initials: YY
authors.lastname: Choi
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.|Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jae Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyunki
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.|Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Moon Hee
authors.initials: MH
authors.lastname: Sim
authors.affiliation: Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Ka-Kyung
authors.initials: KK
authors.lastname: Kim
authors.affiliation: Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Gunho
authors.initials: G
authors.lastname: Lee
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyoung-Il
authors.initials: HI
authors.lastname: Kim
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.|Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
authors.forename: Ji Yeong
authors.initials: JY
authors.lastname: An
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Woo Jin
authors.initials: WJ
authors.lastname: Hyung
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Choong-Bai
authors.initials: CB
authors.lastname: Kim
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Noh
authors.affiliation: Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sangwoo
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.|Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul, Korea.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.|Department of Biochemistry &Molecular Biology, Yonsei University College of Medicine, Seoul, Korea.|Open NBI Convergence Technology Research Laboratory of Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Cheong
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D059472:Exome; D005260:Female; D023281:Genomics; D064593:Heterografts; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*