中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Establishment of a hepatocellular carcinoma patient-derived xenograft platform and its application in biomarker identification

文献类型:期刊论文

AuthorHu, Bo2,3; Guo, Wei2,3; Sun, Yun-Fan2,3; Zhang, Xin2,3; Tang, Wei-Guo2,3; Yang, Liu-Xiao2,3; Xu, Yang2,3; Qiu, Shuang-Jian2,3; Zhou, Jian2,3; Fan, Jia2,3,5
SourceINTERNATIONAL JOURNAL OF CANCER
Issued Date2019
Volume146Issue:6Pages:1606-1617
Keywordhepatocellular carcinoma patient-derived tumor grafts sorafenib drug resistance
ISSN0020-7136
DOI10.1002/ijc.32564
SubtypeArticle
English AbstractUsing a method optimized in hepatocellular carcinoma (HCC), we established patient-derived xenograft (PDX) models with an increased take rate (42.2%) and demonstrated that FBS +10% dimethyl sulfoxide exhibited the highest tumor take rate efficacy. Among 254 HCC patients, 103 stably transplantable xenograft lines that could be serially passaged, cryopreserved and revived were established. These lines maintained the diversity of HCC and the essential features of the original specimens at the histological, transcriptome, proteomic and genomic levels. Tumor engraftment was associated with lack of encapsulation, poor tumor differentiation, large size and overexpression of cancer stem cell biomarkers, and was an independent predictor for overall survival and tumor recurrence after resection. To confirm the preclinical value of the PDX model in HCC treatment, several antitumor agents were tested in 16 selected PDX models. The results revealed a high degree of pharmacologic heterogeneity in the cohort, as well as heterogeneity to different agents in the same individual. The sorafenib responses observed between HCC patients and the corresponding PDXs were also consistent. After molecular characterization of the PDX models, we explored the predictive markers for sorafenib response and found that mitogen-activated protein kinase kinase kinase 1 (MAP3K1) might play an important role in sorafenib resistance and sorafenib response is impaired in patients with MAP3K1 downexpression. Our results indicated that PDX models could accurately reproduce patient tumors biology and could aid in the discovery of new treatments to advance in precision medicine.
SubjectOncology
WOS KeywordTUMOR XENOGRAFTS ; MOUSE MODELS ; LARGE PANEL ; EXPRESSION ; CELLS ; HETEROGENEITY ; THERAPEUTICS ; SORAFENIB ; PREDICT ; TRENDS
Language英语
PublisherWILEY
WOS IDWOS:000481071500001
Version出版稿
源URL[http://202.127.25.144/handle/331004/531]  
Collection中国科学院上海生命科学研究院营养科学研究所
Affiliation1.Fudan Univ, Zhongshan Hosp, Dept Lab Med, Shanghai, Peoples R China;
2.Fudan Univ, Zhongshan Hosp, Liver Canc Inst, Dept Liver Surg, Shanghai, Peoples R China;
3.Minist Educ, Key Lab Carcinogenesis & Canc Invas, Shanghai, Peoples R China;
4.Chinese Acad Sci, Key Lab Computat Biol, CAS MPG Partner Inst Computat Biol, Shanghai Inst Biol Sci, Shanghai, Peoples R China;
5.Fudan Univ, Inst Biomed Sci, Shanghai, Peoples R China,
Recommended Citation
GB/T 7714
Hu, Bo,Guo, Wei,Sun, Yun-Fan,et al. Establishment of a hepatocellular carcinoma patient-derived xenograft platform and its application in biomarker identification[J]. INTERNATIONAL JOURNAL OF CANCER,2019,146(6):1606-1617.
APA Hu, Bo.,Guo, Wei.,Sun, Yun-Fan.,Zhang, Xin.,Tang, Wei-Guo.,...&,.(2019).Establishment of a hepatocellular carcinoma patient-derived xenograft platform and its application in biomarker identification.INTERNATIONAL JOURNAL OF CANCER,146(6),1606-1617.
MLA Hu, Bo,et al."Establishment of a hepatocellular carcinoma patient-derived xenograft platform and its application in biomarker identification".INTERNATIONAL JOURNAL OF CANCER 146.6(2019):1606-1617.

入库方式: OAI收割

来源:上海营养与健康研究所

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