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

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)216-225
Number of pages10
JournalMetabolomics
Volume4
Issue number3
DOIs
StatePublished - Jul 2 2008

Fingerprint

Cachexia
Metabolomics
Glycosylation
Muscle
VLDL Lipoproteins
Lipids
LDL Lipoproteins
Glucose
Tumors
Bearings (structural)
Dystroglycans
Neoplasms
Ubiquitin-Protein Ligases
Biomarkers
Tumor Biomarkers
Regression analysis
Statistical methods
Blood
Nuclear magnetic resonance
Metabolome

Keywords

  • Cachexia
  • Cancer
  • Metabolomics
  • Metabonomics
  • Murine model
  • NMR spectroscopy

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Clinical Biochemistry

Cite this

O'Connell, T. M., Ardeshirpour, F., Asher, S. A., Winnike, J. H., Yin, X., George, J., ... Couch, M. E. (2008). Metabolomic analysis of cancer cachexia reveals distinct lipid and glucose alterations. Metabolomics, 4(3), 216-225. https://doi.org/10.1007/s11306-008-0113-7

Metabolomic analysis of cancer cachexia reveals distinct lipid and glucose alterations. / O'Connell, Thomas M.; Ardeshirpour, Farhad; Asher, Scott A.; Winnike, Jason H.; Yin, Xiaoying; George, Jonathan; Guttridge, Denis C.; He, Wei; Wysong, Ashley; Willis, Monte S.; Couch, Marion E.

In: Metabolomics, Vol. 4, No. 3, 02.07.2008, p. 216-225.

Research output: Contribution to journalArticle

O'Connell, TM, Ardeshirpour, F, Asher, SA, Winnike, JH, Yin, X, George, J, Guttridge, DC, He, W, Wysong, A, Willis, MS & Couch, ME 2008, 'Metabolomic analysis of cancer cachexia reveals distinct lipid and glucose alterations', Metabolomics, vol. 4, no. 3, pp. 216-225. https://doi.org/10.1007/s11306-008-0113-7
O'Connell TM, Ardeshirpour F, Asher SA, Winnike JH, Yin X, George J et al. Metabolomic analysis of cancer cachexia reveals distinct lipid and glucose alterations. Metabolomics. 2008 Jul 2;4(3):216-225. https://doi.org/10.1007/s11306-008-0113-7
O'Connell, Thomas M. ; Ardeshirpour, Farhad ; Asher, Scott A. ; Winnike, Jason H. ; Yin, Xiaoying ; George, Jonathan ; Guttridge, Denis C. ; He, Wei ; Wysong, Ashley ; Willis, Monte S. ; Couch, Marion E. / Metabolomic analysis of cancer cachexia reveals distinct lipid and glucose alterations. In: Metabolomics. 2008 ; Vol. 4, No. 3. pp. 216-225.
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