Time-Course Changes in Potential Biomarkers Detected Using a Metabonomic Approach in Walker 256 Tumor-Bearing Rats
Time-Course Changes in Potential Biomarkers Detected Using a Metabonomic Approach in Walker 256 Tumor-Bearing Rats
复制标题
使用代谢组学方法在 Walker 256 只荷瘤大鼠中检测到潜在生物标志物的时程变化
DOI：
10.1021/pr101198q
复制
发表时间：
2011-04-01
影响因子：
4.4
通讯作者：
Abliz, Zeper
中科院分区：
文献类型：
--
作者：
Shen, Guoqing;Chen, Yanhua;Abliz, Zeper
采用基于互补亲水相互作用色谱和反相液相色谱的代谢组学方法，结合串联质谱和代谢产物的时程分析，在步行者256只荷瘤大鼠的尿液中寻找更可靠的潜在生物标志物。代谢组学的一个主要挑战是区分与疾病的发生和进展密切相关的可靠生物标志物与那些无关但显著改变的生物标志物。本研究根据肿瘤发生、发展过程中代谢产物的变化趋势，筛选出了这些生物标志物。从接种前至接种后16天连续采集7批尿样进行分析。多变量分析显示87个鉴别代谢物。通过对代谢产物进行时程分析，筛选出变化规律合理的生物标志物。共分离出47个化合物，鉴定出15个化合物，其中肉毒碱类12个，氨基酸类2个，核苷类1个。基于这些潜在生物标志物的时程行为，我们假设这种破坏可能是由于细胞增殖增加、脂肪酸β氧化减少和肾小管重吸收不良所致。这些研究表明，这种方法可以帮助寻找更可靠的潜在生物标志物，并为荷瘤生物系统的代谢改变提供有价值的生化见解。
A metabonomic approach based on complementary hydrophilic interaction chromatography and reversed-phase liquid chromatography combined with tandem mass spectrometry and time-course analysis of metabolites was implemented to find more reliable potential biomarkers in urine of Walker 256 tumor-bearing rats. A major challenge in metabonomics is distinguishing reliable biomarkers that are closely associated with the genesis and progression of diseases from those that are unrelated but altered significantly. In this study, these biomarkers were selected according to the change trends of discriminating metabolites during the genesis and progression of cancer. Seven consecutive batches of urine samples from preinoculation to 16 days after were collected and analyzed. Multivariate analysis revealed 87 discriminating metabolites. Time-course analysis of discriminating metabolites was used to select more reliable biomarkers with regular and reasonable change trends. Finally, 47 were found and 15 were identified including 12 carnitine derivatives, 2 amino acid derivatives, 1 nucleoside. On the basis of time-course behaviors of these potential biomarkers, we hypothesize such disruption might result from elevated cell proliferation, reduced beta-oxidation of fatty acids, and poor renal tubular reabsorption. These studies demonstrate that this method can help to find more reliable potential biomarkers and provide valuable biochemical insights into metabolic alterations in tumor-bearing biosystems.