Metabolite profiling of human colon carcinoma - Deregulation of TCA cycle and amino acid turnover

Carsten Denkert, Jan Budczies, Wilko Weichert, Gert Wohlgemuth, Martin Scholz, Tobias Kind, Silvia Niesporek, Aurelia Noske, Anna Buckendahl, Manfred Dietel, Oliver Fiehn

Research output: Contribution to journalArticle

224 Citations (Scopus)

Abstract

Background: 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. Results: 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. Conclusion: 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.

Original languageEnglish (US)
Article number72
JournalMolecular Cancer
Volume7
DOIs
StatePublished - Sep 18 2008

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Colon
Carcinoma
Amino Acids
Metabolomics
Colonic Neoplasms
Colorectal Neoplasms
Pyrimidines
Purines
Passive Cutaneous Anaphylaxis
Molecular Pathology
Genomics
Metabolic Networks and Pathways
Gas Chromatography
Proteomics
Urea
Mass Spectrometry
Neoplasms
Mucous Membrane
Databases
Phenotype

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Oncology

Cite this

Denkert, C., Budczies, J., Weichert, W., Wohlgemuth, G., Scholz, M., Kind, T., ... Fiehn, O. (2008). Metabolite profiling of human colon carcinoma - Deregulation of TCA cycle and amino acid turnover. Molecular Cancer, 7, [72]. https://doi.org/10.1186/1476-4598-7-72

Metabolite profiling of human colon carcinoma - Deregulation of TCA cycle and amino acid turnover. / Denkert, Carsten; Budczies, Jan; Weichert, Wilko; Wohlgemuth, Gert; Scholz, Martin; Kind, Tobias; Niesporek, Silvia; Noske, Aurelia; Buckendahl, Anna; Dietel, Manfred; Fiehn, Oliver.

In: Molecular Cancer, Vol. 7, 72, 18.09.2008.

Research output: Contribution to journalArticle

Denkert, C, Budczies, J, Weichert, W, Wohlgemuth, G, Scholz, M, Kind, T, Niesporek, S, Noske, A, Buckendahl, A, Dietel, M & Fiehn, O 2008, 'Metabolite profiling of human colon carcinoma - Deregulation of TCA cycle and amino acid turnover', Molecular Cancer, vol. 7, 72. https://doi.org/10.1186/1476-4598-7-72
Denkert, Carsten ; Budczies, Jan ; Weichert, Wilko ; Wohlgemuth, Gert ; Scholz, Martin ; Kind, Tobias ; Niesporek, Silvia ; Noske, Aurelia ; Buckendahl, Anna ; Dietel, Manfred ; Fiehn, Oliver. / Metabolite profiling of human colon carcinoma - Deregulation of TCA cycle and amino acid turnover. In: Molecular Cancer. 2008 ; Vol. 7.
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