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Molecular phenotypes reveal heterogeneous engraftments of patient-derived hepatocellular carcinoma xenografts

摘要Objective:Patient-derived xenograft(PDX)models provide a promising preclinical platform for hepatocellular carcinoma(HCC).However,the molecular features associated with successful engraftment of PDX models have not been revealed.Methods:HCC tumor samples from 76 patients were implanted in immunodeficient mice.The molecular expression was evaluated by immunohistochemistry.Patient and tumor characteristics as well as tumor molecular expressions were compared for PDX engraftment using the Chi-square test.The independent prediction parameters were identified by logistic regression analyses.Results:The engraftment rate for PDX models from patients with HCC was 39.47%(30/76).Tumors from younger patients and patients with elevated preoperative alpha-fetoprotein level had higher engraftment rates.Tumors with poor differentiation and vascular invasion were related to engraftment success.The positive expression of CK19,CD133,glypican-3(GPC3),and Ki67 in tumor samples was associated with engraftment success.Logistic regression analyses indicated that GPC3 and Ki67 were two of the strongest predictors of PDX engraftment.Tumors with GPC3/Ki67 phenotypes showed heterogeneous engraftment rates,with 71.9%in GPC3+/Ki67+tumors,30.8%in GPC3-/Ki67+tumors,15.0%in GPC3+/Ki67-tumors,and 0 in GPC3-/Ki67-tumors.Conclusions:Successful engraftment of HCC PDXs was significantly related to molecular features.Tumors with the GPC3+/Ki67* phenotype were the most likely to successfully establish HCC PDXs.

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作者 Jianyong Zhuo [1] Di Lu [2] Jianguo Wang [2] Zhengxing Lian [3] Jiali Zhang [3] Huihui Li [3] Beini Cen [3] Xuyong Wei [2] Qiang Wei [2] Haiyang Xie [3] Xiao Xu [1] 学术成果认领
作者单位 Department of Hepatobiliary and Pancreatic Surgery,The Center for Integrated Oncology and Precision Medicine,Affiliated Hangzhou First People's Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China;Department of Hepatobiliary and Pancreatic Surgery,the First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China;National Health Commission Key Laboratory of Combined Multi-organ Transplantation [1] Department of Hepatobiliary and Pancreatic Surgery,The Center for Integrated Oncology and Precision Medicine,Affiliated Hangzhou First People's Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China [2] National Health Commission Key Laboratory of Combined Multi-organ Transplantation [3]
栏目名称 Original Article
DOI 10.21147/j.issn.1000-9604.2021.04.04
发布时间 2021-10-13
基金项目
This study was supported by grants from the National Science and Technology Major Project of China the National Natural Science Funds for Distinguished Young Scholar of China Key Program National Natural Science Foundation of China and Key Research&Development Plan of Zhejiang Province
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中国癌症研究(英文版)

中国癌症研究(英文版)

2021年33卷4期

470-479页

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