Metabolomics

, 4:216

Metabolomic analysis of cancer cachexia reveals distinct lipid and glucose alterations

  • Thomas M. O’Connell
  • Farhad Ardeshirpour
  • Scott A. Asher
  • Jason H. Winnike
  • Xiaoying Yin
  • Jonathan George
  • Denis C. Guttridge
  • Wei He
  • Ashley Wysong
  • Monte S. Willis
  • Marion E. Couch
Original Article

Abstract

Cancer cachexia remains a challenging clinical problem with complex pathophysiology and unreliable diagnostic tools. A blood test to detect this metabolic derangement would aid in early treatment of these patients. A 1H NMR-based metabolomics approach was used to determine the unique metabolic fingerprint of cachexia and to search for biomarkers in serum samples taken from an established murine model of cancer cachexia. Male CD2F1 mice received a subcutaneous flank injection of C26 adenocarcinoma cells to induce experimental cancer-related cachexia. Two molecular markers of muscle atrophy, upregulation of the E3 ubiquitin ligase Muscle Ring Finger 1 (MuRF1) and aberrant glycosylation of β-dystroglycan (β-DG), were used to confirm muscle wasting in the tumor-bearing mice. Serum samples were collected for metabolomic analysis during the development of the cachexia: at baseline, when the tumor was palpable, and when the mice demonstrated cachexia. The unsupervised statistical analysis demonstrated a distinct metabolic profile with the onset of cachexia. The critical metabolic changes associated with cachexia included increased levels of very low density lipoprotein (VLDL) and low density lipoprotein (LDL), with decreased serum glucose levels. Regression analysis demonstrated a very high correlation of the presence of aberrant glycosylation of β-DG with the unique metabolic profile of cachexia. This study demonstrates for the first time that metabolomics has potential as a diagnostic tool in cancer cachexia, and in further elucidating simultaneous metabolic pathway alterations due to this syndrome. In addition, variations in VLDL and LDL deserve more investigation as surrogate serum biomarkers for cancer cachexia.

Keywords

Metabolomics Cancer Cachexia NMR spectroscopy Murine model Metabonomics 

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Thomas M. O’Connell
    • 1
    • 2
  • Farhad Ardeshirpour
    • 3
  • Scott A. Asher
    • 4
  • Jason H. Winnike
    • 5
  • Xiaoying Yin
    • 4
    • 6
  • Jonathan George
    • 3
    • 7
  • Denis C. Guttridge
    • 8
  • Wei He
    • 8
  • Ashley Wysong
    • 7
    • 9
  • Monte S. Willis
    • 10
  • Marion E. Couch
    • 4
    • 6
  1. 1.Division of Pharmacotherapy and Experimental TherapeuticsUniversity of North Carolina School of PharmacyChapel HillUSA
  2. 2.Department of Biomedical EngineeringUniversity of North CarolinaChapel HillUSA
  3. 3.The Verne S. Caviness General Clinical Research CenterUniversity of North Carolina School of MedicineChapel HillUSA
  4. 4.Department of Otolaryngology-Head & Neck SurgeryUniversity of North Carolina School of Medicine, G0412 Neurosciences HospitalChapel HillUSA
  5. 5.Department of Biomedical EngineeringUniversity of North CarolinaChapel HillUSA
  6. 6.The Lineberger Comprehensive Cancer CenterUniversity of North Carolina School of MedicineChapel HillUSA
  7. 7.Duke University School of MedicineDurhamUSA
  8. 8.Division of Human Cancer Genetics, Department of Molecular Virology, Immunology and Medical Genetics, Integrated Biomedical Graduate Program, Department of Pathology, and The Arthur G. James Comprehensive Cancer CenterThe Ohio State UniversityColumbusUSA
  9. 9.University of North Carolina School of MedicineChapel HillUSA
  10. 10.Department of Pathology and Laboratory MedicineUniversity of North Carolina School of MedicineChapel HillUSA

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