Metabolite profiling of human colon carcinoma--deregulation of TCA cycle and amino acid turnover.
Metabolite profiling of human colon carcinoma--deregulation of TCA cycle and amino acid turnover.
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DOI：
10.1186/1476-4598-7-72
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发表时间：
2008-09-18
期刊：
影响因子：
37.3
通讯作者：
Fiehn O
中科院分区：
文献类型：
--
作者：
Denkert C;Budczies J;Weichert W;Wohlgemuth G;Scholz M;Kind T;Niesporek S;Noske A;Buckendahl A;Dietel M;Fiehn O
除基因改变外，结直肠癌的发生和发展与营养摄入、营养过剩和细胞代谢变化的影响有关，这可能是新的诊断和治疗方法的基础。然而，与基因组学和蛋白质组学相比，恶性肿瘤中代谢组学变化的全面研究很少进行。在这项研究中，我们用气相色谱-飞行时间质谱法研究了一组正常结肠组织和结直肠癌组织的配对样本，结果检测到总共206种代谢物。对于无监督PCA分析的前两个组成部分，结肠癌和正常组织的代谢表型在Bonferroni校正显著水平p = 0.00170和p = 0.00005上是不同的。随后的监督分析发现82种代谢物差异显著，p < 0.01。通过一种计算KEGG数据库相互作用晶格中每对代谢物的距离的新方法，代谢物与代谢途径中的异常联系起来。TCA循环的中间产物和脂质在癌症中被发现下调，而尿素循环代谢物、嘌呤、嘧啶和氨基酸的水平普遍高于正常结肠粘膜。本研究表明，代谢谱在高显著水平上促进了正常和肿瘤结肠组织的生化表型，并指出基于gc - tof的代谢组学是分子病理学研究的新方法。
Apart from genetic alterations, development and progression of colorectal cancer has been linked to influences from nutritional intake, hyperalimentation, and cellular metabolic changes that may be the basis for new diagnostic and therapeutic approaches. However, in contrast to genomics and proteomics, comprehensive metabolomic investigations of alterations in malignant tumors have rarely been conducted. In this study we investigated a set of paired samples of normal colon tissue and colorectal cancer tissue with gas-chromatography time-of-flight mass-spectrometry, which resulted in robust detection of a total of 206 metabolites. Metabolic phenotypes of colon cancer and normal tissues were different at a Bonferroni corrected significance level of p = 0.00170 and p = 0.00005 for the first two components of an unsupervised PCA analysis. Subsequent supervised analysis found 82 metabolites to be significantly different at p < 0.01. Metabolites were connected to abnormalities in metabolic pathways by a new approach that calculates the distance of each pair of metabolites in the KEGG database interaction lattice. Intermediates of the TCA cycle and lipids were found down-regulated in cancer, whereas urea cycle metabolites, purines, pyrimidines and amino acids were generally found at higher levels compared to normal colon mucosa. This study demonstrates that metabolic profiling facilitates biochemical phenotyping of normal and neoplastic colon tissue at high significance levels and points to GC-TOF-based metabolomics as a new method for molecular pathology investigations.
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影响因子：
46.9
作者：
Fiehn, O;Kopka, J;Willmitzer, L
通讯作者：
Willmitzer, L
影响因子：
168.9
作者：
Michiels, S;Koscielny, S;Hill, C
通讯作者：
Hill, C
影响因子：
5.9
作者：
Cousins, Robert J.
通讯作者：
Cousins, Robert J.
DOI：
10.1073/pnas.0503955102
发表时间：
2005-10-04
影响因子：
11.1
作者：
Catchpole, GS;Beckmann, M;Draper, J
通讯作者：
Draper, J
影响因子：
5.8
作者：
Kose, F;Weckwerth, W;Fiehn, O
通讯作者：
Fiehn, O