Integrated metabolomic profiling of hepatocellular carcinoma in hepatitis C cirrhosis through GC/MS and UPLC/MS-MS.
Integrated metabolomic profiling of hepatocellular carcinoma in hepatitis C cirrhosis through GC/MS and UPLC/MS-MS.
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DOI：
10.1111/liv.12541
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发表时间：
2014-10
期刊：
影响因子：
--
通讯作者：
Cabrera R
中科院分区：
文献类型：
--
作者：
Fitian AI;Nelson DR;Liu C;Xu Y;Ararat M;Cabrera R
与肝细胞癌（HCC）相关的代谢途径紊乱仍然不能令人满意的特点。确定与HCC存在相关的代谢改变可以提高我们对这种癌症的病理生理学的理解，并可能为改善HCC发展风险患者的疾病监测提供机会。采用气相色谱/质谱（GC/MS）和超高效液相色谱/电喷雾串联质谱（UPLC/MS-MS）的综合非靶向代谢组学方法，表征与丙型肝炎（HCV）相关肝硬化引起的HCC相关的总体代谢改变。使用结合两种代谢组学平台GC/MS和UPLC/MS-MS的代谢组学方法表征30名HCC患者、27名丙型肝炎肝硬化疾病对照和30名健康志愿者的总体血清代谢组。进行多变量统计和受试者操作者特征分析，以确定HCC患者与HCV患者相比最显著改变的代谢物。肝硬化对照，因此表现出与HCC的存在密切相关。升高的12-羟基二十碳四烯酸（12-HETE）、15-HETE、鞘氨醇、γ-谷氨酰氧化应激相关代谢物、黄嘌呤、氨基酸丝氨酸、甘氨酸和天冬氨酸以及α-环肉碱与HCC的存在密切相关。胆汁酸和二羧酸的升高与肝硬化高度相关。通过GC/MS和UPLC/MS-MS的综合代谢组学分析确定了HCC和HCV肝硬化的总体代谢紊乱。异常的氨基酸生物合成、细胞更新调节、活性氧中和和类花生酸途径可能是HCC的标志。二羧酸代谢异常、胆汁酸代谢增强和纤维蛋白原裂解肽升高可能是肝硬化的特征。
The metabolic pathway disturbances associated with hepatocellular carcinoma (HCC) remain unsatisfactorily characterized. Determination of the metabolic alterations associated with the presence of HCC can improve our understanding of the pathophysiology of this cancer and may provide opportunities for improved disease monitoring of patients at risk for HCC development. To characterize the global metabolic alterations associated with HCC arising from hepatitis C (HCV)-associated cirrhosis using an integrated non-targeted metabolomics methodology employing both gas chromatography/mass spectrometry (GC/MS) and ultrahigh-performance liquid chromatography/electrospray ionization tandem mass spectrometry (UPLC/MS-MS). The global serum metabolomes of 30 HCC patients, 27 hepatitis C cirrhosis disease controls and 30 healthy volunteers were characterized using a metabolomics approach that combined two metabolomics platforms, GC/MS and UPLC/MS-MS. Random forest, multivariate statistics and receiver operator characteristic analysis were performed to identify the most significantly altered metabolites in HCC patients vs. HCV-cirrhosis controls and which therefore exhibited a close association with the presence of HCC. Elevated 12-hydroxyeicosatetraenoic acid (12-HETE), 15-HETE, sphingosine, γ-glutamyl oxidative stress-associated metabolites, xanthine, amino acids serine, glycine and aspartate, and a-cylcarnitines were strongly associated with the presence of HCC. Elevations in bile acids and dicarboxylic acids were highly correlated with cirrhosis. Integrated metabolomic profiling through GC/MS and UPLC/MS-MS identified global metabolic disturbances in HCC and HCV-cirrhosis. Aberrant amino acid biosynthesis, cell turnover regulation, reactive oxygen species neutralization and eicosanoid pathways may be hallmarks of HCC. Aberrant dicarboxylic acid metabolism, enhanced bile acid metabolism and elevations in fibrinogen cleavage peptides may be signatures of cirrhosis.
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影响因子：
7.4
作者：
Marra M;Sordelli IM;Lombardi A;Lamberti M;Tarantino L;Giudice A;Stiuso P;Abbruzzese A;Sperlongano R;Accardo M;Agresti M;Caraglia M;Sperlongano P
通讯作者：
Sperlongano P
影响因子：
6.2
作者：
Cao, Hongcui;Huang, Haijun;Li, Lanjuan
通讯作者：
Li, Lanjuan
15-脂氧合酶-1/15-羟基二十碳四烯酸通过蛋白激酶B和热休克蛋白90复合物激活促进肝细胞癌细胞生长
DOI：
10.1016/j.biocel.2013.02.018
发表时间：
2013-06-01
影响因子：
4
作者：
Ma, Jun;Zhang, Lei;Zhu, Daling
通讯作者：
Zhu, Daling
影响因子：
13.5
作者：
Beyoglu, Diren;Imbeaud, Sandrine;Maurhofer, Olivier;Bioulac-Sage, Paulette;Zucman-Rossi, Jessica;Dufour, Jean-Francois;Idle, Jeffrey R.
通讯作者：
Idle, Jeffrey R.
谷胱甘肽 S-转移酶 P1 与肝细胞癌氧化应激相关
影响因子：
3.6
作者：
Li T;Zhao XP;Wang LY;Gao S;Zhao J;Fan YC;Wang K
通讯作者：
Wang K