Molecular liver cancer prevention in cirrhosis by organ transcriptome analysis and lysophosphatidic acid pathway inhibition

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...

Descripción completa

Detalles Bibliográficos
Autores: 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
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2016
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/128127
Acceso en línea:https://hdl.handle.net/2445/128127
Access Level:acceso abierto
Palabra clave:Càncer de fetge
Cirrosi hepàtica
Liver cancer
Hepatic cirrhosis
Descripción
Sumario: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.

Similares en LA Referencia