Ibarra R, Dazard J-E, Sandlers Y, Rehman F, Abbas R, Kombu R, Zhang G-F, Brunengraber H, Sanabria J
Departments of Surgery, Case Western Reserve University, School of Medicine and University Hospitals, Case Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA ; Departments of Nutrition, Case Western Reserve University, School of Medicine and University Hospitals, Case Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
Center for Proteomics and Bioinformatics, Case Western Reserve University, School of Medicine and University Hospitals, Case Medical Center, Cleveland, OH 44106, USA.
HPB Surg. 2014;2014:310372. doi: 10.1155/2014/310372. Epub 2014 Mar 2.
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.
目的。在美国，肝脏肿瘤的发病率正在上升。本研究的目的是确定癌症早期发展过程中肝脏组织的代谢谱。方法。我们使用兔VX2肝肿瘤模型（LT）和一个对照组，该对照组由向肝脏植入明胶海绵的假手术动物组成（LG）。植入后两周，从实验动物（LT+/LT-）的有肿瘤和无肿瘤叶获取肝脏组织，以及从对照组（LG+/LG-）获取肝脏组织。对气相色谱 - 质谱法获得的峰进行鉴定。鉴定出56种代谢物，并使用主成分分析（PCA）和混合效应双向方差分析模型比较各组之间的代谢谱。结果。动物术后恢复顺利。分析确定了在控制错误发现率（FDR）后，实验条件下有显著差异的代谢物谱。比较（LT+/LT-）的样本与（LG+/LG-）肝脏的样本时，16种代谢物浓度有显著差异。比较（LT+）肝叶的样本与（LT-）肝叶的样本时，20种代谢物也有显著差异。结论。含有恶性肿瘤的正常肝脏组织具有独特的代谢特征。代谢谱在肝脏活检检测早期肝癌中的作用仍有待确定。
