Metabolite profiling of human colon carcinoma--deregulation of TCA cycle and amino acid turnover.
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.
Denkert
Carsten
C
Institute of Pathology, Charité University Hospital, 10117 Berlin, Germany. carsten.denkert@charite.de
Budczies
Jan
J
Weichert
Wilko
W
Wohlgemuth
Gert
G
Scholz
Martin
M
Kind
Tobias
T
Niesporek
Silvia
S
Noske
Aurelia
A
Buckendahl
Anna
A
Dietel
Manfred
M
Fiehn
Oliver
O
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
D000596:Amino Acids
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