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| Status |
Public on Dec 16, 2016 |
| Title |
Transcriptome profiles of cirrhotic liver treated with lysophosphatidic acid pathway inhibitors |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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 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, reverse-engineering precision cancer prevention.
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| Overall design |
Cirrhosis-driven hepatocellular carcinoma (HCC) was induced in rats by weekly administration of low-dose diethylnitrosamine (low-dose DEN rat). HCC chemopreventive effects of lysophosphatidic acid (LPA) pathway inhibitors, AM063 (autotaxin [ATX] inhibitor) and AM095 (LPA receptor 1 [LPAR1] inhibitor), was examined.
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| Contributor(s) |
Nakagawa S, Wei L, Song W, Sun X, Venkatesh A, Goossens N, Koh AP, Tanabe KK, Fuchs BC, Hoshida Y |
| Citation(s) |
27960085 |
| Submission date |
Sep 11, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Yujin Hoshida |
| E-mail(s) |
Yujin.Hoshida@UTSouthwestern.edu
|
| Organization name |
University of Texas Southwestern Medical Center
|
| Street address |
5323 Harry Hines Blvd
|
| City |
Dallas |
| State/province |
TX |
| ZIP/Postal code |
75390 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL14844 |
Illumina HiSeq 2000 (Rattus norvegicus) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE64520 |
Molecular liver cancer prevention in cirrhosis by organ transcriptome analysis and lysophosphatidic acid pathway inhibition |
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| Relations |
| SRA |
SRP063345 |
| BioProject |
PRJNA295963 |
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