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.

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
• 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