Metabolomics

, 4:216

Metabolomic analysis of cancer cachexia reveals distinct lipid and glucose alterations

Authors

  • Thomas M. O’Connell
    • Division of Pharmacotherapy and Experimental TherapeuticsUniversity of North Carolina School of Pharmacy
    • Department of Biomedical EngineeringUniversity of North Carolina
  • Farhad Ardeshirpour
    • The Verne S. Caviness General Clinical Research CenterUniversity of North Carolina School of Medicine
  • Scott A. Asher
    • Department of Otolaryngology-Head & Neck SurgeryUniversity of North Carolina School of Medicine, G0412 Neurosciences Hospital
  • Jason H. Winnike
    • Department of Biomedical EngineeringUniversity of North Carolina
  • Xiaoying Yin
    • Department of Otolaryngology-Head & Neck SurgeryUniversity of North Carolina School of Medicine, G0412 Neurosciences Hospital
    • The Lineberger Comprehensive Cancer CenterUniversity of North Carolina School of Medicine
  • Jonathan George
    • The Verne S. Caviness General Clinical Research CenterUniversity of North Carolina School of Medicine
    • Duke University School of Medicine
  • Denis C. Guttridge
    • 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 University
  • Wei He
    • 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 University
  • Ashley Wysong
    • Duke University School of Medicine
    • University of North Carolina School of Medicine
  • Monte S. Willis
    • Department of Pathology and Laboratory MedicineUniversity of North Carolina School of Medicine
    • Department of Otolaryngology-Head & Neck SurgeryUniversity of North Carolina School of Medicine, G0412 Neurosciences Hospital
    • The Lineberger Comprehensive Cancer CenterUniversity of North Carolina School of Medicine
Original Article

DOI: 10.1007/s11306-008-0113-7

Cite this article as:
O’Connell, T.M., Ardeshirpour, F., Asher, S.A. et al. Metabolomics (2008) 4: 216. doi:10.1007/s11306-008-0113-7

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

Copyright information

© Springer Science+Business Media, LLC 2008