| Literature DB >> 27960085 |
Shigeki Nakagawa1, Lan Wei2, Won Min Song3, Takaaki Higashi1, Sarani Ghoshal2, Rosa S Kim4, C Billie Bian4, Suguru Yamada2, Xiaochen Sun4, Anu Venkatesh4, Nicolas Goossens5, Gretchen Bain6, Gregory Y Lauwers7, Anna P Koh4, Mohamed El-Abtah4, Noor B Ahmad4, Hiroki Hoshida4, Derek J Erstad2, Ganesh Gunasekaran8, Youngmin Lee4, Ming-Lung Yu9, Wan-Long Chuang10, Chia-Yen Dai10, Masahiro Kobayashi11, Hiromitsu Kumada11, Toru Beppu12, Hideo Baba12, Milind Mahajan13, Venugopalan D Nair14, Michael Lanuti15, Augusto Villanueva4, Angelo Sangiovanni16, Massimo Iavarone16, Massimo Colombo16, Josep M Llovet17, Aravind Subramanian18, Andrew M Tager19, Scott L Friedman4, Thomas F Baumert20, Myron E Schwarz8, Raymond T Chung21, Kenneth K Tanabe2, Bin Zhang13, Bryan C Fuchs22, Yujin Hoshida23.
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.Entities:
Keywords: cancer chemoprevention; gene signature; hepatocellular carcinoma; prognostic prediction; transcriptome
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Year: 2016 PMID： 27960085 PMCID： PMC5161110 DOI： 10.1016/j.ccell.2016.11.004
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 38.585