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- W4361259433 abstract "<div>Abstract<p>Nonalcoholic steatohepatitis (NASH) is a common preneoplastic condition of hepatocellular carcinoma (HCC). Mice with hepatocytic deletion of <i>Pten</i> develop NASH and HCC later in life. This model is highly valuable for studies aimed at identifying the molecular mechanism by which metabolic disorders contribute to tumor development. We applied proteomic and lipidomic profiling approaches to <i>Pten</i>-null NASH liver and tumors. Circulating fatty acid composition was also characterized in these mice. The relevance to human NASH and HCC was further validated. This integrative proteomic and lipidomic study from mouse to human and from liver to blood identified the following disease signatures: (i) an HCC signature: upregulated hepatic scd1/scd2, fads2, and acsl5:acsl1 ratio, elevated vaccenic and erucic acids, and reduced margaric and linoleic acids in both liver and plasma; (ii) a NASH signature that correlates with tumor burden: upregulated hepatic elovl6, elevated oleic, adrenic, and osbond acids, and reduced cervonic acid in liver and plasma; and (iii) a NASH signature: reduced hepatic and circulating lignoceric and eicosapentaenoic acids. Altogether, these results show the role of lipid-modifying enzymes converting saturated fatty acids (SFA) to monounsaturated fatty acids (MUFA) in HCC and the importance of an increased ratio of long chain n6-polyunsaturated fatty acids over n3-polyunsaturated fatty acids in NASH and HCC risk. They also highlight the relevance of the <i>Pten</i>-null model for studies related to NASH and HCC and show that circulating lipid metabolome provides a direct read of lipid changes in the liver. Most importantly, novel candidate targets for HCC diagnosis, therapy, risk assessment, and prevention were identified. <i>Cancer Res; 73(15); 4722–31. ©2013 AACR</i>.</p></div>" @default.
- W4361259433 created "2023-03-31" @default.
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- W4361259433 date "2023-03-30" @default.
- W4361259433 modified "2023-09-25" @default.
- W4361259433 title "Data from Proteomic and Lipidomic Signatures of Lipid Metabolism in NASH-Associated Hepatocellular Carcinoma" @default.
- W4361259433 doi "https://doi.org/10.1158/0008-5472.c.6504615" @default.
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