Circulating sphingosine-1-phosphate and erythrocyte sphingosine kinase-1 activity as novel biomarkers for early prostate cancer detection
Open Access
- 7 February 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in British Journal of Cancer
- Vol. 106 (5), 909-915
- https://doi.org/10.1038/bjc.2012.14
Abstract
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. 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) (n=110) or with young healthy males with the very small chance of having PCa foci (n=20). Levels of circulating S1P were significantly higher in healthy subjects (10.36±0.69 pmol per mg protein, PP=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. 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.Keywords
This publication has 31 references indexed in Scilit:
- Circulating sphingolipid biomarkers in models of type 1 diabetesJournal of Lipid Research, 2011
- Sphingosine kinase-1 activity and expression in human prostate cancer resection specimensEuropean Journal of Cancer, 2010
- Absolute and Relative Risk of Cardiovascular Disease in Men With Prostate Cancer: Results From the Population-Based PCBaSe SwedenJournal of Clinical Oncology, 2010
- Inflammatory cytokines and aromatase inhibitor-associated musculoskeletal syndrome: a case–control studyBritish Journal of Cancer, 2010
- Sphingosine kinase 1 inhibition sensitizes hormone‐resistant prostate cancer to docetaxelInternational Journal of Cancer, 2009
- Vascular Endothelium As a Contributor of Plasma Sphingosine 1-PhosphateCirculation Research, 2008
- Microarray analysis of altered sphingolipid metabolism reveals prognostic significance of sphingosine kinase 1 in breast cancerBreast Cancer Research and Treatment, 2007
- Sphingosine Kinase-1 as a Chemotherapy Sensor in Prostate Adenocarcinoma Cell and Mouse ModelsCancer Research, 2005
- Overcoming MDR-associated chemoresistance in HL-60 acute myeloid leukemia cells by targeting shingosine kinase-1Leukemia, 2005
- Predicting obstructive coronary artery disease with serum sphingosine-1-phosphateAmerican Heart Journal, 2003