Department of Hepatobiliary Surgery, Tianjin Third Central Hospital, Tianjin 300170, China.
World J Gastroenterol. 2013 Jun 14;19(22):3423-32. doi: 10.3748/wjg.v19.i22.3423.
To select characteristic endogenous metabolites in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients and to identify their molecular mechanism and potential clinical value.
An ultra performance liquid chromatography and linear trap quadrupole-Orbitrap XL-mass spectrometry platform was used to analyze endogenous metabolites in the homogenate of central tumor tissue, adjacent tissue and distant tissue obtained from 10 HBV-related HCC patients. After pretreatment with Mzmine software, including peak detection, alignment and normalization, the acquired data were treated with Simca-P+software to establish multivariate statistical analysis based on a pattern recognition technique and characteristic metabolites highly correlated with changing trends in metabolic profiling were selected and further identified.
Based on data acquired using Mzmine software, a principal component analysis model (R2X = 66.9%, Q2 = 21.7%) with 6 principal components and an orthogonal partial least squares discriminant analysis model (R2X = 76.5%, R2Y = 93.7%, Q2 = 68.7%) with 2 predicted principal components and 5 orthogonal principal components were established in the three tissue groups. Forty-nine ions were selected, 33 ions passed the 2 related samples nonparametric test (P < 0.05) and 14 of these were further identified as characteristic metabolites that showed significant differences in levels between the central tumor tissue group and distant tumor tissue group, including 9 metabolites (L-phenylalanine, glycerophosphocholine, lysophosphatidylcholines, lysophosphatidylethanolamines and chenodeoxycholic acid glycine conjugate) which had been reported as serum metabolite biomarkers for HCC diagnosis in previous research, and 5 metabolites (beta-sitosterol, quinaldic acid, arachidyl carnitine, tetradecanal, and oleamide) which had not been reported before.
Characteristic metabolites and metabolic pathways highly related to HCC pathogenesis and progression are identified through metabolic profiling analysis of HCC tissue homogenates.
筛选乙型肝炎病毒(HBV)相关肝细胞癌(HCC)患者的特征内源性代谢物,并鉴定其分子机制和潜在的临床价值。
采用超高效液相色谱-线性阱轨道阱 XL 质谱平台分析 10 例 HBV 相关 HCC 患者中心肿瘤组织、相邻组织和远处组织匀浆中的内源性代谢物。经 Mzmine 软件预处理,包括峰检测、对齐和归一化后,采用 Simca-P+软件对所获得的数据进行多元统计分析,基于模式识别技术建立基于模型,并选择与代谢谱变化趋势高度相关的特征代谢物,并进一步进行鉴定。
基于 Mzmine 软件获得的数据,建立了 3 组组织的主成分分析模型(R2X = 66.9%,Q2 = 21.7%),包含 6 个主成分和正交偏最小二乘判别分析模型(R2X = 76.5%,R2Y = 93.7%,Q2 = 68.7%),包含 2 个预测主成分和 5 个正交主成分。共筛选出 49 个离子,33 个离子通过 2 个相关样本非参数检验(P < 0.05),其中 14 个被进一步鉴定为中央肿瘤组织组与远处肿瘤组织组之间水平差异显著的特征代谢物,包括 9 个代谢物(L-苯丙氨酸、甘油磷酸胆碱、溶血磷脂酰胆碱、溶血磷脂酰乙醇胺和鹅去氧胆酸甘氨酸结合物),这些代谢物曾被报道为 HCC 诊断的血清代谢物生物标志物,以及 5 个以前未报道过的代谢物(β-谷甾醇、喹哪啶酸、花生四烯基肉碱、十四醛和油酰胺)。
通过 HCC 组织匀浆代谢组学分析,鉴定出与 HCC 发病机制和进展高度相关的特征代谢物和代谢途径。