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Cited 10 time in webofscience Cited 10 time in scopus
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Integrated Genomic Comparison of Mouse Models Reveals Their Clinical Resemblance to Human Liver Canceropen access

Authors
Yim, Sun YoungShim, Jae-JunShin, Ji-HyunJeong, Yun SeongKang, Sang-HeeKim, Sang-BaeEun, Young GyuLee, Dong JinConner, Elizabeth A.Factor, Valentina M.Moore, David D.Johnson, Randy L.Thorgeirsson, Snorri S.Lee, Ju-Seog
Issue Date
Nov-2018
Publisher
AMER ASSOC CANCER RESEARCH
Citation
MOLECULAR CANCER RESEARCH, v.16, no.11, pp.1713 - 1723
Indexed
SCIE
SCOPUS
Journal Title
MOLECULAR CANCER RESEARCH
Volume
16
Number
11
Start Page
1713
End Page
1723
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/2948
DOI
10.1158/1541-7786.MCR-18-0313
ISSN
1541-7786
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.
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2. Clinical Science > Department of Colon and Rectal Surgery > 1. Journal Articles
2. Clinical Science > Department of Gastroenterology and Hepatology > 1. Journal Articles

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Kang, Sang hee
구로병원 (Department of Colon and Rectal Surgery, Guro Hospital)
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