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Molecular phenotypes reveal heterogeneous engraftments of patient-derived hepatocellular carcinoma xenografts
Authors:Jianyong Zhuo  Di Lu  Jianguo Wang  Zhengxing Lian  Jiali Zhang  Huihui Li  Beini Cen  Xuyong Wei  Qiang Wei  Haiyang Xie  Xiao Xu
Abstract:ObjectivePatient-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.MethodsHCC 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.ResultsThe 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. ConclusionsSuccessful 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.
Keywords:Hepatocellular carcinoma   patient-derived xenografts   heterogeneous establishment   molecular phenotype
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