Urinary diagnostic proteomic markers for dynapenia in cancer patients

  • Authors:
    • Holger Husi
    • Alisdair MacDonald
    • Richard J.E Skipworth
    • Janice Miller
    • Andrew Cronshaw
    • Carolyn Greig
    • Kenneth C.H. Fearon
    • James A. Ross
  • View Affiliations

  • Published online on: April 25, 2018     https://doi.org/10.3892/br.2018.1092
  • Pages: 547-556
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Abstract

Dynapenia is defined as the age‑related loss of muscle strength, and plays a significant role in the loss of physical function and increased risk of disability among older individuals. The need for an early diagnosis supports the search for a biomarker that reflects muscle ‘weakening’. This has previously proven difficult due to patient heterogeneity at presentation and lack of understanding of the underlying molecular mechanisms. The aim of the present study was to identify potential urinary biomarkers of dynapenia in patients undergoing potentially curative surgery for upper gastro­intestinal cancer. Maximum isometric knee extensor strength (strain gauge) and maximum leg extensor power (Nottingham power rig) measurements were taken. Cut‑off values for dynapenia were based on the Allied Dunbar national fitness survey. Values below the 5th percentile for the population matched for age and sex on the Allied Dunbar national fitness survey were used to stratify the cohort into dynapenic or normal. Urine samples taken at induction of anaesthesia were analysed by SELDI‑TOF mass spectrometry using CM10 and IMAC30 chip‑types to establish statistically significant m/z peak fingerprint patterns, followed by in‑gel LC‑MS/MS to identify molecular constituents. Statistical analysis of decision‑tree calculations using Biomarker Pattern software resulted in models with sensitivities of 86 and 96%, specificities of 81 and 89%, and overall correctness of 84 and 93%, when applied to the entire cohort for power and strength measurement‑based stratifications using the IMAC30 chip‑type and the CM10 chip‑type, respectively. The molecular identities of 10 peaks of interest were further investigated. After subtraction of potentially unrelated proteins, they were identified as fragments of Annexin A1, collagen α‑1 (XV), perlecan and myotrophin. These results demonstrate that urinary screening can be used to define cancer‑associated muscle weakness, and the identification of potential biomarkers could be invaluable in establishing a rapid test to measure and assess dynapenia in the clinical setting.
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June-2018
Volume 8 Issue 6

Print ISSN: 2049-9434
Online ISSN:2049-9442

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Spandidos Publications style
Husi H, MacDonald A, Skipworth RJ, Miller J, Cronshaw A, Greig C, Fearon KC and Ross JA: Urinary diagnostic proteomic markers for dynapenia in cancer patients. Biomed Rep 8: 547-556, 2018
APA
Husi, H., MacDonald, A., Skipworth, R.J., Miller, J., Cronshaw, A., Greig, C. ... Ross, J.A. (2018). Urinary diagnostic proteomic markers for dynapenia in cancer patients. Biomedical Reports, 8, 547-556. https://doi.org/10.3892/br.2018.1092
MLA
Husi, H., MacDonald, A., Skipworth, R. J., Miller, J., Cronshaw, A., Greig, C., Fearon, K. C., Ross, J. A."Urinary diagnostic proteomic markers for dynapenia in cancer patients". Biomedical Reports 8.6 (2018): 547-556.
Chicago
Husi, H., MacDonald, A., Skipworth, R. J., Miller, J., Cronshaw, A., Greig, C., Fearon, K. C., Ross, J. A."Urinary diagnostic proteomic markers for dynapenia in cancer patients". Biomedical Reports 8, no. 6 (2018): 547-556. https://doi.org/10.3892/br.2018.1092