Title |
Molecular Liver Cancer Prevention in Cirrhosis by Organ Transcriptome Analysis and Lysophosphatidic Acid Pathway Inhibition
|
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Published in |
Cancer Cell, December 2016
|
DOI | 10.1016/j.ccell.2016.11.004 |
Pubmed ID | |
Authors |
Shigeki Nakagawa, Lan Wei, Won Min Song, Takaaki Higashi, Sarani Ghoshal, Rosa S. Kim, C. Billie Bian, Suguru Yamada, Xiaochen Sun, Anu Venkatesh, Nicolas Goossens, Gretchen Bain, Gregory Y. Lauwers, Anna P. Koh, Mohamed El-Abtah, Noor B. Ahmad, Hiroki Hoshida, Derek J. Erstad, Ganesh Gunasekaran, Youngmin Lee, Ming-Lung Yu, Wan-Long Chuang, Chia-Yen Dai, Masahiro Kobayashi, Hiromitsu Kumada, Toru Beppu, Hideo Baba, Milind Mahajan, Venugopalan D. Nair, Michael Lanuti, Augusto Villanueva, Angelo Sangiovanni, Massimo Iavarone, Massimo Colombo, Josep M. Llovet, Aravind Subramanian, Andrew M. Tager, Scott L. Friedman, Thomas F. Baumert, Myron E. Schwarz, Raymond T. Chung, Kenneth K. Tanabe, Bin Zhang, Bryan C. Fuchs, Yujin Hoshida, on behalf of the Precision Liver Cancer Prevention Consortium |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 6 | 32% |
United Kingdom | 3 | 16% |
Japan | 1 | 5% |
Canada | 1 | 5% |
Unknown | 8 | 42% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 9 | 47% |
Scientists | 7 | 37% |
Science communicators (journalists, bloggers, editors) | 2 | 11% |
Practitioners (doctors, other healthcare professionals) | 1 | 5% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 1 | <1% |
Unknown | 196 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 37 | 19% |
Student > Ph. D. Student | 29 | 15% |
Student > Bachelor | 21 | 11% |
Student > Master | 15 | 8% |
Other | 14 | 7% |
Other | 47 | 24% |
Unknown | 34 | 17% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 42 | 21% |
Medicine and Dentistry | 40 | 20% |
Agricultural and Biological Sciences | 27 | 14% |
Pharmacology, Toxicology and Pharmaceutical Science | 10 | 5% |
Engineering | 9 | 5% |
Other | 23 | 12% |
Unknown | 46 | 23% |