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Metabolomic Analysis of Liver Tissue from the VX2 Rabbit Model of Secondary Liver Tumors

机译:VX2兔继发性肝肿瘤模型肝组织的代谢组学分析

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Purpose.The incidence of liver neoplasms is rising in USA. The purpose of this study was to determine metabolic profiles of liver tissue during early cancer development.Methods.We used the rabbit VX2 model of liver tumors (LT) and a control group consisting of sham animals implanted with Gelfoam into their livers (LG). After two weeks from implantation, liver tissue from lobes with and without tumor was obtained from experimental animals (LT+/LT−) as well as liver tissue from controls (LG+/LG−). Peaks obtained by Gas Chromatography-Mass Spectrometry were subjected to identification. 56 metabolites were identified and their profiles compared between groups using principal component analysis (PCA) and a mixed-effect two-way ANOVA model.Results.Animals recovered from surgery uneventfully. Analyses identified a metabolite profile that significantly differs in experimental conditions after controlling the False Discovery Rate (FDR). 16 metabolites concentrations differed significantly when comparing samples from (LT+/LT−) to samples from (LG+/LG−) livers. A significant difference was also shown in 20 metabolites when comparing samples from (LT+) liver lobes to samples from (LT−) liver lobes.Conclusion.Normal liver tissue harboring malignancy had a distinct metabolic signature. The role of metabolic profiles on liver biopsies for the detection of early liver cancer remains to be determined.
机译:目的:在美国,肝肿瘤的发病率正在上升。本研究的目的是确定早期癌症发展过程中肝脏组织的代谢情况。方法:我们使用了兔肝肿瘤VX2模型(LT)和由假胶动物向其肝脏(LG)植入的假动物组成的对照组。植入后两周,从实验动物(LT + / LT-)以及有对照组的肝组织(LG + / LG-)获得有或没有肿瘤的小叶肝组织。通过气相色谱-质谱法获得的峰进行鉴定。使用主成分分析(PCA)和混合效应双向ANOVA模型,鉴定了56种代谢物,并比较了各组之间的分布图。结果,动物从手术中恢复得很顺利。分析确定了在控制错误发现率(FDR)后在实验条件下存在显着差异的代谢物谱。当比较(LT + / LT-)肝脏样品和(LG + / LG-)肝脏样品时,16种代谢物的浓度差异显着。当比较(LT +)肝叶的样本和(LT-)肝叶的样本时,在20种代谢产物中也显示出显着差异。结论。具有恶性肿瘤的正常肝组织具有独特的代谢特征。代谢谱在肝活检中检测早期肝癌的作用仍有待确定。

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