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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 / Cancer Research Campaign, 106(5), (909-915). doi:10.1038/bjc.2012.14. ISSN 0007-0920

Journal Article Type Article
Acceptance Date Jan 10, 2012
Online Publication Date Feb 7, 2012
Publication Date Feb 28, 2012
Publicly Available Date Nov 30, -0001
Journal British journal of cancer
Print ISSN 0007-0920
Electronic ISSN 1532-1827
Publisher Cancer Research UK
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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Publisher Licence URL
http://creativecommons.org/licenses/by-sa/3.0/





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