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Get Free AccessCirrhosis 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.
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 E. El-Abtah, Noor Banihashem Ahmad, Hiroki Hoshida, Derek J. Erstad, Ganesh Gunasekaran, Young Min 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 Schwarz, Raymond T. Chung, Kenneth K. Tanabe, Bin Zhang, Bryan C. Fuchs, Yujin Hoshida (2016). Molecular Liver Cancer Prevention in Cirrhosis by Organ Transcriptome Analysis and Lysophosphatidic Acid Pathway Inhibition. Cancer Cell, 30(6), pp. 879-890, DOI: 10.1016/j.ccell.2016.11.004.
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Type
Article
Year
2016
Authors
45
Datasets
0
Total Files
0
Language
English
Journal
Cancer Cell
DOI
10.1016/j.ccell.2016.11.004
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