Journal
CANCER CELL
Volume 30, Issue 6, Pages 879-890Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2016.11.004
Keywords
-
Categories
Funding
- Uehara Memorial Foundation
- FLAGS foundation
- Nuovo-Soldati Cancer Research Foundation
- Geneva University Hospital
- Kaohsiung Medical University [KMU-TP103E06, KMU-TP103E07, KMU-TP103E08]
- Kaohsiung Medical University Hospital [KMUH102-2T01]
- ARC, Paris
- Institut Hospitalo-Universitaire, Strasbourg [IHUARC IHU201301187]
- Laboratory of Excellence HEPSYS [ANR-10-LABX-0028]
- European Union [ERC-2014-AdG-671231-HEPCIR]
- NIH/NIDDK [DK078772, DK098079, DK104956, DK099558]
- NIH/NCI [CA140861]
- American Institute for Cancer Research
- Irma T. Hirschl Trust
- Dr. Harold and Golden Lamport Research Award
- U.S. Department of Defense [W81XWH-16-1-0363]
- ICREA Funding Source: Custom
- Agence Nationale de la Recherche (ANR) [ANR-10-LABX-0028] Funding Source: Agence Nationale de la Recherche (ANR)
Ask authors/readers for more resources
Cirrhosis is a milieu that develops hepatocellular carcinoma (HCC), the second most lethal cancer worldwide. HCC prediction and prevention in cirrhosis are key unmet medical needs. Here we have established an HCC risk gene signature applicable to all major HCC etiologies: hepatitis B/C, alcohol, and non-alcoholic steatohepatitis. A transcriptome meta-analysis of >500 human cirrhotics revealed global regulatory gene modules driving HCC risk and the lysophosphatidic acid pathway as a central chemoprevention target. Pharmacological inhibition of the pathway in vivo reduced tumors and reversed the gene signature, which was verified in organotypic ex vivo culture of patient-derived fibrotic liver tissues. These results demonstrate the utility of clinical organ transcriptome to enable a strategy, namely, reverse-engineering precision cancer prevention.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available