title: Metabolite profiling of human colon carcinoma--deregulation of TCA cycle and amino acid turnover.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Pathology, Charité University Hospital, 10117 Berlin, Germany. carsten.denkert@charite.de
authors.forename: Carsten
authors.initials: C
authors.lastname: Denkert
authors.forename: Jan
authors.initials: J
authors.lastname: Budczies
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
authors.forename: Gert
authors.initials: G
authors.lastname: Wohlgemuth
authors.forename: Martin
authors.initials: M
authors.lastname: Scholz
authors.forename: Tobias
authors.initials: T
authors.lastname: Kind
authors.forename: Silvia
authors.initials: S
authors.lastname: Niesporek
authors.forename: Aurelia
authors.initials: A
authors.lastname: Noske
authors.forename: Anna
authors.initials: A
authors.lastname: Buckendahl
authors.forename: Manfred
authors.initials: M
authors.lastname: Dietel
authors.forename: Oliver
authors.initials: O
authors.lastname: Fiehn
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D001706:Biopsy; D002849:Chromatography, Gas; D002952:Citric Acid Cycle; D016000:Cluster Analysis; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D003628:Database Management Systems; D006801:Humans; D005810:Multigene Family
chemical_list: D000596:Amino Acids
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