Article | Published:

Molecular Diagnostics

Alterations in serum amino-acid profile in the progression of colorectal cancer: associations with systemic inflammation, tumour stage and patient survival

British Journal of Cancervolume 120pages238246 (2019) | Download Citation

Abstract

Background

Cancer cachexia is a complex wasting syndrome affecting patients with advanced cancer, with systemic inflammation as a key component in pathogenesis. Protein degradation and release of amino acids (AAs) in skeletal muscle are stimulated in cachexia. Here, we define factors contributing to serum AA levels in colorectal cancer (CRC).

Methods

Serum levels of nine AAs were characterised in 336 CRC patients and their relationships with 20 markers of systemic inflammatory reaction, clinicopathological features of cancers and patient survival were analysed.

Results

Low serum glutamine and histidine levels and high phenylalanine levels associated with indicators of systemic inflammation, including high modified Glasgow Prognostic Score, high blood neutrophil/lymphocyte ratio and high serum levels of CRP, IL-6 and IL-8. Low levels of serum glutamine, histidine, alanine and high glycine levels also associated with advanced cancer stage and with poor cancer-specific survival in univariate analysis.

Conclusions

In CRC, serum AA levels are associated with systemic inflammation and disease stage. These findings may reflect muscle catabolism induced by systemic inflammation in CRC.

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Acknowledgements

We thank Ms. Riitta Vuento for her excellent assistance in the preparation of the study material. This work was supported by grants from Thelma Mäkikyrö Foundation, Emil Aaltonen Foundation, Finnish Cancer Society, K. Albin Johansson Foundation and Orion Research Foundation.

Author information

Affiliations

  1. Cancer and Translational Medicine Research Unit, University of Oulu, POB 5000, 90014, Oulu, Finland

    • Päivi Sirniö
    • , Juha P. Väyrynen
    • , Ilkka Minkkinen
    • , Markus J. Mäkinen
    • , Tuomo J. Karttunen
    •  & Anne Tuomisto
  2. Oulu University Hospital and Medical Research Center Oulu, POB 21, 90029, Oulu, Finland

    • Päivi Sirniö
    • , Juha P. Väyrynen
    • , Kai Klintrup
    • , Jyrki Mäkelä
    • , Karl-Heinz Herzig
    • , Ilkka Minkkinen
    • , Markus J. Mäkinen
    • , Tuomo J. Karttunen
    •  & Anne Tuomisto
  3. Research Unit of Surgery, Anesthesia and Intensive Care, University of Oulu, POB 5000, 90014, Oulu, Finland

    • Kai Klintrup
    •  & Jyrki Mäkelä
  4. Department of Physiology, Research Unit of Biomedicine and Biocenter Oulu, University of Oulu, POB 5000, 90014, Oulu, Finland

    • Toni Karhu
    •  & Karl-Heinz Herzig
  5. Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, ul. Szpitalna 27/33, 60-572, Poznan, Poland

    • Karl-Heinz Herzig

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Contributions

Study conception and design: P. Sirniö, J.P. Väyrynen, A. Tuomisto. Data collection: P. Sirniö, J.P. Väyrynen, K. Klintrup, J. Mäkelä, T. Karhu, K.-H. Herzig, I. Minkkinen, M.J. Mäkinen, T.J. Karttunen, A. Tuomisto. Statistical analysis: P. Sirniö, J.P. Väyrynen, A. Tuomisto. Manuscript draft: P. Sirniö, J. P. Väyrynen, A. Tuomisto. Manuscript review and editing: P. Sirniö, J.P. Väyrynen, K. Klintrup, J. Mäkelä, T. Karhu, K.-H. Herzig, I. Minkkinen, M.J. Mäkinen, T. J. Karttunen, A. Tuomisto.

Compliance with ethical standards:

 The study was approved by the Ethical Committee of Oulu University Hospital (58/2005, 184/2009) and was performed in accordance with the Declaration of Helsinki. All patients had signed an informed consent to participate.

Data availability

The data sets generated and analysed during the current study are available from the corresponding author on reasonable request.

Conflict of interest

The authors declare that they have no conflict of interest.

Note

This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).

Corresponding author

Correspondence to Anne Tuomisto.

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DOI

https://doi.org/10.1038/s41416-018-0357-6