PDF(Pubmed)
Abstract：
In pre-disposed individuals, a reprogramming of the hepatic lipid metabolism may support liver cancer initiation. We conducted a high-resolution mass spectrometry based untargeted lipidomics analysis of pre-diagnostic serum samples from a nested case-control study (219 liver cancer cases and 219 controls) within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Out of 462 annotated lipids, 158 (34.2%) were associated with liver cancer risk in a conditional logistic regression analysis at a false discovery rate (FDR) <0.05. A chemical set enrichment analysis (ChemRICH) and co-regulatory set analysis suggested that 22/28 lipid classes and 47/83 correlation modules were significantly associated with liver cancer risk (FDR <0.05). Strong positive associations were observed for monounsaturated fatty acids (MUFA), triacylglycerols (TAGs) and phosphatidylcholines (PCs) having MUFA acyl chains. Negative associations were observed for sphingolipids (ceramides and sphingomyelins), lysophosphatidylcholines, cholesterol esters and polyunsaturated fatty acids (PUFA) containing TAGs and PCs. Stearoyl-CoA desaturase enzyme 1 (SCD1), a rate limiting enzyme in fatty acid metabolism and ceramidases seems to be critical in this reprogramming. In conclusion, our study reports pre-diagnostic lipid changes that provide novel insights into hepatic lipid metabolism reprogramming may contribute to a pro-cell growth and anti-apoptotic tissue environment and, in turn, support liver cancer initiation.
摘要：
在有偏见的个人中，肝脏脂质代谢的重编程可能支持肝癌的发生。我们对来自巢式病例对照研究（219例肝癌病例和219例对照）的α-生育酚的诊断前血清样品进行了基于高分辨率质谱的非靶向脂质组学分析。β-胡萝卜素癌症预防（ATBC）研究。在462个注释的脂质中，158（34.2％）在条件逻辑回归分析中与肝癌风险相关，错误发现率（FDR）<0.05。化学集富集分析（ChemRICH）和共调控集分析表明，22/28脂质类别和47/83相关模块与肝癌风险显着相关（FDR<0.05）。单不饱和脂肪酸（MUFA）观察到强烈的正相关，具有MUFA酰基链的三酰基甘油(TAG)和磷脂酰胆碱(PC)。观察到鞘脂（神经酰胺和鞘磷脂）的负相关，溶血磷脂酰胆碱，胆固醇酯和含有TAG和PC的多不饱和脂肪酸（PUFA）。硬脂酰辅酶A去饱和酶1(SCD1),脂肪酸代谢中的限速酶和神经酰胺酶似乎在这种重编程中至关重要。总之,我们的研究报告了诊断前的脂质变化，提供了新的见解肝脂质代谢重编程可能有助于促进细胞生长和抗凋亡组织环境，反过来,支持肝癌的启动。
