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Circulating sphingosine-1-phosphate and erythrocyte sphingosine kinase-1 activity as novel biomarkers for early prostate cancer detection

Nunes, J.; Naymark, M.; Sauer, L.; Muhammad, A.; Keun, H.; Sturge, J.; Stebbing, J.; Waxman, J.; Pchejetski, D.

Authors

J. Nunes

M. Naymark

L. Sauer

A. Muhammad

H. Keun

J. Stebbing

J. Waxman

D. Pchejetski



Abstract

Background: Current markers available for screening normal populations and for monitoring prostate cancer (PCa) treatment lack sensitivity and selectivity. Sphingosine-1-phosphate (S1P) is a circulating lipid second messenger involved in cell growth and migration, the immune response, angiogenesis, and malignant transformation.Methods:Eighty-eight patients with localised, locally advanced, or metastatic PCa were recruited into this prospective single-centre study. Plasma S1P levels were measured and compared with age-matched controls with benign prostate hyperplasia (BPH) (n110) or with young healthy males with the very small chance of having PCa foci (n=20).Results:Levels of circulating S1P were significantly higher in healthy subjects (10.36±0.69 pmol per mg protein, P < 0.0001) and patients with BPH (9.39±0.75, P=0.0013) than in patients with PCa (6.89±0.58, ANOVA, P=0.0019). Circulating S1P levels were an early marker of PCa progression to hormonal unresponsiveness and correlated with prostate-specific antigen (PSA) levels and lymph node metastasis. During the course of the study, nine patients have died of PCa. Importantly, their circulating S1P levels were significantly lower (5.11±0.75) than in the surviving patients (7.02±0.22, n=79, P=0.0439). Our data suggest that the decrease in circulating S1P during PCa progression may stem from a highly significant downregulation of erythrocyte sphingosine kinase-1 (SphK1) activity (2.14±0.17 pmol per mg protein per minute in PCa patients vs 4.7±0.42 in healthy individuals, P=0.0001), which may be a potential mechanism of cancer-induced anaemia. Conclusion: This current study has provided a potential mechanism for cancer-related anaemia and the first evidence that plasma S1P and erythrocyte SphK1 activity are the potential markers for the diagnosis, monitoring, and predicating for PCa mortality. © 2012 Cancer Research UK All rights reserved.

Citation

Nunes, J., Naymark, M., Sauer, L., Muhammad, A., Keun, H., Sturge, J., …Pchejetski, D. (2012). Circulating sphingosine-1-phosphate and erythrocyte sphingosine kinase-1 activity as novel biomarkers for early prostate cancer detection. The British Journal of Cancer, 106(5), 909-915. https://doi.org/10.1038/bjc.2012.14

Journal Article Type Article
Acceptance Date Jan 10, 2012
Online Publication Date Feb 7, 2012
Publication Date Feb 28, 2012
Publicly Available Date Jul 27, 2018
Journal British journal of cancer
Print ISSN 0007-0920
Electronic ISSN 1532-1827
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 106
Issue 5
Pages 909-915
DOI https://doi.org/10.1038/bjc.2012.14
Keywords Prostate cancer; Molecular marker; Diagnosis; Prognosis; Sphingosine-1-phosphate; Anaemia
Public URL https://hull-repository.worktribe.com/output/417735
Publisher URL http://www.nature.com/bjc/journal/v106/n5/full/bjc201214a.html

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