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Cancer cachexia’s metabolic signature in a murine model confirms a distinct entity

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Abstract

Despite recent consensus definitions, lack of specific biomarkers remains a hurdle towards a more accurate and efficient diagnosis of cancer cachexia, distinguishing cachexia as a separate entity from other wasting syndromes. In a previous pilot study, we have shown that cancer-cachectic mice have a unique metabolic fingerprint with distinct glucose and lipid alterations compared to healthy controls. Further metabolomics studies were carried out to investigate differences in metabolic profiles of cancer-cachectic mice to tumor-bearing non-cachectic mice, calorie-restricted mice, and surgically treated cancer-cachectic mice. CD2F1 mice were divided into: (1) Cachexia Group received cachexia-inducing C26 undifferentiated colon carcinoma cells; (2) Tumor-Burden Group received, non-cachectic, P388 lymphoma cells; (3) Caloric-Restriction Group, remaining cancer-free, but subjected to caloric-restriction; (4) Surgery Group, similar to Cachexia Group, but tumors resected mid-experiment; and (5) Control Group aged intact. Baseline, mid-experiment and final serum samples were collected for 1H NMR spectroscopic analysis. After data reduction, unsupervised principal component analysis and orthogonal projections to latent structures analyses demonstrate that the unique metabolic fingerprint is independent of tumor-burden and distinct from profiles of caloric-restriction and aging. Hyperlipidemia, hyperglycemia, and reduced branched-chain amino acids distinguish cachexia from other groups. Furthermore, the profile of surgically treated mice differs from that of cachectic mice, reverting to a profile more congruent with healthy controls indicating cachexia is amenable to correction where surgical cure is possible. That metabolomic analysis of murine serum is able to differentiate cachexia from tumor-burden and caloric-restriction warrants similar translational investigations in patients to explore cancer cachexia’s unique biomarkers.

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Acknowledgments

J. Walter Juckett postdoctoral fellowship (H.D.); National Institutes of Health T32 training grant (S.A.); University of North Carolina Program in Translational Science grant (M.C.); General Clinical Research Center grant #RR000046 (T.O.); and National Institute of Environmental Health Sciences grant P30ES10126 (T.O.).

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Authors and Affiliations

  1. Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Vermont, Fletcher 301, 111 Colchester Ave, Burlington, VT, 05401, USA

    Hirak Der-Torossian & Marion E. Couch

  2. Vermont Cancer Center, University of Vermont, Burlington, VT, USA

    Hirak Der-Torossian & Marion E. Couch

  3. Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Alabama, Birmingham, AL, USA

    Scott A. Asher

  4. David H. Murdock Research Institute, North Carolina Research Campus, Kannapolis, NC, USA

    Jason H. Winnike

  5. Department of Dermatology, Stanford University, Stanford, CA, USA

    Ashley Wysong

  6. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA

    Xiaoying Yin

  7. Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA

    Monte S. Willis

  8. LipoScience Inc., Raleigh, NC, USA

    Thomas M.  O’Connell

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  1. Hirak Der-Torossian
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  2. Scott A. Asher
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  3. Jason H. Winnike
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  5. Xiaoying Yin
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  6. Monte S. Willis
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  7. Thomas M.  O’Connell
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  8. Marion E. Couch
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Correspondence to Marion E. Couch.

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Der-Torossian, H., Asher, S.A., Winnike, J.H. et al. Cancer cachexia’s metabolic signature in a murine model confirms a distinct entity. Metabolomics 9, 730–739 (2013). https://doi.org/10.1007/s11306-012-0485-6

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  • DOI: https://doi.org/10.1007/s11306-012-0485-6

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