Back to Search
Start Over
Biomarkers of coordinate metabolic reprogramming in colorectal tumors in mice and humans.
- Source :
-
Gastroenterology [Gastroenterology] 2014 May; Vol. 146 (5), pp. 1313-24. Date of Electronic Publication: 2014 Jan 15. - Publication Year :
- 2014
-
Abstract
- Background & Aims: There are no robust noninvasive methods for colorectal cancer screening and diagnosis. Metabolomic and gene expression analyses of urine and tissue samples from mice and humans were used to identify markers of colorectal carcinogenesis.<br />Methods: Mass spectrometry-based metabolomic analysis of urine and tissues from wild-type C57BL/6J and Apc(Min/+) mice, as well as from mice with azoxymethane-induced tumors, was employed in tandem with gene expression analysis. Metabolic profiling was also performed on colon tumor and adjacent nontumor tissues from 39 patients. The effects of β-catenin activity on metabolic profiles were assessed in mice with colon-specific disruption of Apc.<br />Results: Thirteen markers were found in urine associated with development of colorectal tumors in Apc(Min/+) mice. Metabolites related to polyamine metabolism, nucleic acid metabolism, and methylation, identified tumor-bearing mice with 100% accuracy, and also accurately identified mice with polyps. Changes in gene expression in tumor samples from mice revealed that derangement of metabolites were a reflection of coordinate metabolic reprogramming in tumor tissue. Similar changes in urinary metabolites were observed in mice with azoxymethane-induced tumors and in mice with colon-specific activation of β-catenin. The metabolic alterations indicated by markers in urine, therefore, appear to occur during early stages of tumorigenesis, when cancer cells are proliferating. In tissues from patients, tumors had stage-dependent increases in 17 metabolites associated with the same metabolic pathways identified in mice. Ten metabolites that were increased in tumor tissues, compared with nontumor tissues (proline, threonine, glutamic acid, arginine, N1-acetylspermidine, xanthine, uracil, betaine, symmetric dimethylarginine, and asymmetric-dimethylarginine), were also increased in urine from tumor-bearing mice.<br />Conclusions: Gene expression and metabolomic profiles of urine and tissue samples from mice with colorectal tumors and of colorectal tumor samples from patients revealed pathways associated with derangement of specific metabolic pathways that are indicative of early-stage tumor development. These urine and tissue markers might be used in early detection of colorectal cancer.<br /> (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Azoxymethane
Biomarkers, Tumor urine
Cell Proliferation
Chromatography, Reverse-Phase
Colorectal Neoplasms chemically induced
Colorectal Neoplasms pathology
Colorectal Neoplasms urine
Disease Models, Animal
Gene Expression Regulation, Neoplastic
Genes, APC
High-Throughput Screening Assays
Humans
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neoplasm Staging
Predictive Value of Tests
Protein Interaction Mapping
Protein Interaction Maps
Real-Time Polymerase Chain Reaction
Reproducibility of Results
Spectrometry, Mass, Electrospray Ionization
Biomarkers, Tumor genetics
Biomarkers, Tumor metabolism
Colorectal Neoplasms genetics
Colorectal Neoplasms metabolism
Gene Expression Profiling methods
Metabolomics methods
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0012
- Volume :
- 146
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 24440673
- Full Text :
- https://doi.org/10.1053/j.gastro.2014.01.017