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Title: | Molecular liver cancer prevention in cirrhosis by organ transcriptome analysis and lysophosphatidic acid pathway inhibition |
Author: | Nakagawa, Shigeki Wei, Lan Song, Won Min Higashi, Takaaki Ghoshal, Sarani Kim, Rosa S. Bian, C. Billie Yamada, Suguru Sun, Xiaochen Venkatesh, Anu Goossens, Nicolas Bain, Gretchen Lauwers, Gregory Y. Koh, A. P. El-Abtah, Mohamed Ahmad, Noor B. Hoshida, Hiroki Erstad, Derek J. Gunasekaran, Ganesh Lee, Youngmin Yu, Ming-Lung Chuang, Wan-Long Dai, Chia-Yen Kobayashi, Masahiro Kumada, Hiromitsu Beppu, Toru Baba, Hideo Mahajan, Milind Nair, Venugopalan D. Lanuti, Michael Villanueva, Augusto Sangiovanni, Angelo Iavarone, Massimo Colombo, Massimo Llovet i Bayer, Josep Maria Subramanian, Aravind Tager, Andrew M. Friedman, Scott L. Baumert, Thomas F. Schwartz, Myron Chung, Raymond T. Tanabe, Kenneth K. Zhang, Bin Fuchs, Bryan C. Hoshida, Yujin Precision Liver Cancer Prevention Consortium |
Keywords: | Càncer de fetge Cirrosi hepàtica Liver cancer Hepatic cirrhosis |
Issue Date: | 2016 |
Publisher: | Elsevier |
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. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1016/j.ccell.2016.11.004 |
It is part of: | Cancer Cell, 2016, vol. 30, num. 6, p. 879-890 |
URI: | http://hdl.handle.net/2445/128127 |
Related resource: | https://doi.org/10.1016/j.ccell.2016.11.004 |
ISSN: | 1535-6108 |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Medicina) |
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