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  3. Biomarkers Of Coordinate Metabolic Reprogramming In Colorectal Tumors In Mice And Humans.
  1. Home
  3. Biomarkers Of Coordinate Metabolic Reprogramming In Colorectal Tumors In Mice And Humans.

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Biomarkers of coordinate metabolic reprogramming in colorectal tumors in mice and humans.

Soumen K Manna1, Naoki Tanaka1, Kristopher W Krausz1

  • 1Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.

Gastroenterology
|January 21, 2014

View abstract on PubMed

Summary
This summary is machine-generated.

Researchers identified key urine and tissue markers for early colorectal cancer detection. These metabolic and gene expression changes in mice and humans indicate early-stage tumor development, paving the way for noninvasive screening.

Keywords:
Apc(Min/+)AzoxymethaneCancer BiomarkerColorectal CancerMetabolic ReprogrammingMetabolomics

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Area of Science:

  • Biochemistry
  • Oncology
  • Genomics

Background:

  • Current noninvasive methods for colorectal cancer screening and diagnosis are limited.
  • Identifying reliable biomarkers is crucial for early detection and improved patient outcomes.

Purpose of the Study:

  • To identify novel noninvasive biomarkers for colorectal cancer using metabolomic and gene expression analyses.
  • To investigate metabolic alterations associated with colorectal carcinogenesis in preclinical models and human patients.

Main Methods:

  • Mass spectrometry-based metabolomic profiling of urine and tissues from wild-type and tumor-bearing mice (Apc(Min/+), azoxymethane-induced tumors).
  • Gene expression analysis of mouse tumor tissues.
  • Metabolic profiling of human colon tumor and adjacent nontumor tissues from 39 patients.
  • Assessment of β-catenin activity effects on metabolic profiles in genetically modified mice.

    • Main Results:

    • Thirteen urinary markers associated with colorectal tumor development were identified in mice, accurately detecting tumors and polyps.
    • Metabolic pathway derangements (polyamine, nucleic acid, methylation) in tumor tissue correlated with urinary metabolite changes.
    • Similar urinary metabolite alterations were observed in different mouse models of colorectal cancer, indicating early-stage tumorigenesis.
    • Seventeen metabolites showed stage-dependent increases in human tumor tissues, mirroring pathways identified in mice. Ten specific metabolites were elevated in both human tumor tissues and mouse urine.

    Conclusions:

    • Metabolomic and gene expression profiles of urine and tissues reveal metabolic pathway derangements indicative of early colorectal tumor development.
    • Identified urine and tissue markers hold potential for the early, noninvasive detection of colorectal cancer.