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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 E.
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:
It is part of: Cancer Cell, 2016, vol. 30, num. 6, p. 879-890
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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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