Molecular Liver Cancer Prevention in Cirrhosis by Organ Transcriptome Analysis and Lysophosphatidic Acid Pathway Inhibition.
Cancer Cell
; 30(6): 879-890, 2016 Dec 12.
Article
in En
| MEDLINE
| ID: mdl-27960085
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Health context:
1_ASSA2030
Database:
MEDLINE
Main subject:
Lysophospholipids
/
Carcinoma, Hepatocellular
/
Gene Expression Profiling
/
Liver Cirrhosis
/
Liver Neoplasms
/
Antineoplastic Agents
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Cancer Cell
Year:
2016
Document type:
Article