Molecular Liver Cancer Prevention in Cirrhosis by Organ Transcriptome Analysis and Lysophosphatidic Acid Pathway Inhibition.
Molecular Liver Cancer Prevention in Cirrhosis by Organ Transcriptome Analysis and Lysophosphatidic Acid Pathway Inhibition.
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DOI：
10.1016/j.ccell.2016.11.004
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发表时间：
2016-12-12
期刊：
影响因子：
50.3
通讯作者：
Precision Liver Cancer Prevention Consortium
中科院分区：
文献类型：
--
作者：
Nakagawa S;Wei L;Song WM;Higashi T;Ghoshal S;Kim RS;Bian CB;Yamada S;Sun X;Venkatesh A;Goossens N;Bain G;Lauwers GY;Koh AP;El-Abtah M;Ahmad NB;Hoshida H;Erstad DJ;Gunasekaran G;Lee Y;Yu ML;Chuang WL;Dai CY;Kobayashi M;Kumada H;Beppu T;Baba H;Mahajan M;Nair VD;Lanuti M;Villanueva A;Sangiovanni A;Iavarone M;Colombo M;Llovet JM;Subramanian A;Tager AM;Friedman SL;Baumert TF;Schwarz ME;Chung RT;Tanabe KK;Zhang B;Fuchs BC;Hoshida Y;Precision Liver Cancer Prevention Consortium
肝硬化是发展肝细胞癌（HCC）的环境，肝细胞癌是世界上第二大致死性癌症。肝硬化的HCC预测和预防是关键的未满足的医疗需求。在此，我们建立了适用于所有主要HCC病因的HCC风险基因标签：B/C型肝炎、酒精和非酒精性脂肪性肝炎。对>500名人类肝癌患者的转录组荟萃分析揭示了驱动HCC风险的全球调控基因模块和溶血磷脂酸途径作为中心化学预防靶点。体内途径的药理学抑制减少了肿瘤并逆转了基因特征，这在源自患者的纤维化肝组织的器官型离体培养中得到了验证。这些结果证明了临床器官转录组的实用性，以实现一种策略，即逆向工程精确预防癌症。
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 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, reverse-engineering precision cancer prevention.
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影响因子：
13.5
作者：
Fuchs, Bryan C.;Hoshida, Yujin;Fujii, Tsutomu;Wei, Lan;Yamada, Suguru;Lauwers, Gregory Y.;McGinn, Christopher M.;DePeralta, Danielle K.;Chen, Xintong;Kuroda, Toshihiko;Lanuti, Michael;Schmitt, Anthony D.;Gupta, Supriya;Crenshaw, Andrew;Onofrio, Robert;Taylor, Bradley;Winckler, Wendy;Bardeesy, Nabeel;Caravan, Peter;Golub, Todd R.;Tanabe, Kenneth K.
通讯作者：
Tanabe, Kenneth K.
影响因子：
168.9
作者：
Cuzick, Jack;Sestak, Ivana;Howell, Anthony
通讯作者：
Howell, Anthony
DOI：
10.1056/nejmoa0804525
发表时间：
2008-11-06
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hoshida Y;Villanueva A;Kobayashi M;Peix J;Chiang DY;Camargo A;Gupta S;Moore J;Wrobel MJ;Lerner J;Reich M;Chan JA;Glickman JN;Ikeda K;Hashimoto M;Watanabe G;Daidone MG;Roayaie S;Schwartz M;Thung S;Salvesen HB;Gabriel S;Mazzaferro V;Bruix J;Friedman SL;Kumada H;Llovet JM;Golub TR
通讯作者：
Golub TR
影响因子：
29.4
作者：
Calvisi, Diego F.;Ladu, Sara;Pascale, Rosa M.
通讯作者：
Pascale, Rosa M.
影响因子：
158.5
作者：
Calle, EE;Rodriguez, C;Thun, MJ
通讯作者：
Thun, MJ