Integrated Genomic Comparison of Mouse Models Reveals Their Clinical Resemblance to Human Liver Cancer
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Yim, Sun Young | - |
dc.contributor.author | Shim, Jae-Jun | - |
dc.contributor.author | Shin, Ji-Hyun | - |
dc.contributor.author | Jeong, Yun Seong | - |
dc.contributor.author | Kang, Sang-Hee | - |
dc.contributor.author | Kim, Sang-Bae | - |
dc.contributor.author | Eun, Young Gyu | - |
dc.contributor.author | Lee, Dong Jin | - |
dc.contributor.author | Conner, Elizabeth A. | - |
dc.contributor.author | Factor, Valentina M. | - |
dc.contributor.author | Moore, David D. | - |
dc.contributor.author | Johnson, Randy L. | - |
dc.contributor.author | Thorgeirsson, Snorri S. | - |
dc.contributor.author | Lee, Ju-Seog | - |
dc.date.available | 2020-11-02T06:55:31Z | - |
dc.date.issued | 2018-11 | - |
dc.identifier.issn | 1541-7786 | - |
dc.identifier.issn | 1557-3125 | - |
dc.identifier.uri | https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/2948 | - |
dc.description.abstract | Hepatocellular carcinoma (HCC) is a heterogeneous disease. Mouse models are commonly used as preclinical models to study hepatocarcinogenesis, but how well these models recapitulate molecular subtypes of human HCC is unclear. Here, integration of genomic signatures from molecularly and clinically defined human HCC (n = 11) and mouse models of HCC (n = 9) identified the mouse models that best resembled subtypes of human HCC and determined the clinical relevance of each model. Mst1/2 knockout (KO), Sav1 KO, and SV40 T antigen mouse models effectively recapitulated subtypes of human HCC with a poor prognosis, whereas the Myc transgenic model best resembled human HCCs with a more favorable prognosis. The Myc model was also associated with activation of beta-catenin. E2f1, E2f1/Myc, E2f1/Tgfa, and diethylnitrosamine (DEN)-induced models were heterogeneous and were unequally split into poor and favor-able prognoses. Mst1/2 KO and Sav1 KO models best resemble human HCC with hepatic stem cell characteristics. Applying a genomic predictor for immunotherapy, the six-gene IFNg score, the Mst1/2 KO, Sav1 KO, SV40, and DEN models were predicted to be the least responsive to immunotherapy. Further analysis showed that elevated expression of immuneinhibitory genes (Cd276 and Nectin2/Pvrl2) in Mst1/2 KO, Sav1 KO, and SV40 models and decreased expression of immune stimulatory gene (Cd86) in the DEN model might be accountable for the lack of predictive response to immunotherapy. Implication: The current genomic approach identified the most relevant mouse models to human liver cancer and suggests immunotherapeutic potential for the treatment of specific subtypes. (C) 2018 AACR. | - |
dc.format.extent | 11 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | AMER ASSOC CANCER RESEARCH | - |
dc.title | Integrated Genomic Comparison of Mouse Models Reveals Their Clinical Resemblance to Human Liver Cancer | - |
dc.type | Article | - |
dc.publisher.location | 미국 | - |
dc.identifier.doi | 10.1158/1541-7786.MCR-18-0313 | - |
dc.identifier.scopusid | 2-s2.0-85055912854 | - |
dc.identifier.wosid | 000448890200009 | - |
dc.identifier.bibliographicCitation | MOLECULAR CANCER RESEARCH, v.16, no.11, pp 1713 - 1723 | - |
dc.citation.title | MOLECULAR CANCER RESEARCH | - |
dc.citation.volume | 16 | - |
dc.citation.number | 11 | - |
dc.citation.startPage | 1713 | - |
dc.citation.endPage | 1723 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.subject.keywordPlus | HUMAN HEPATOCELLULAR-CARCINOMA | - |
dc.subject.keywordPlus | TUMOR-INITIATING CELLS | - |
dc.subject.keywordPlus | HEPATITIS-B-VIRUS | - |
dc.subject.keywordPlus | BETA-CATENIN | - |
dc.subject.keywordPlus | HIPPO-PATHWAY | - |
dc.subject.keywordPlus | TRANSGENIC MICE | - |
dc.subject.keywordPlus | FUNCTIONAL GENOMICS | - |
dc.subject.keywordPlus | PROGENITOR CELLS | - |
dc.subject.keywordPlus | POOR-PROGNOSIS | - |
dc.subject.keywordPlus | ORGAN SIZE | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
73, Goryeodae-ro, Seongbuk-gu, Seoul, Republic of Korea (02841)82-2-2286-1265
COPYRIGHT 2020 KOREA UNIVERSITY MEDICAL LIBRARY ALL RIGHTS RESERVED.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.