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

• Published in: British journal of cancer Vol. 106; no. 5; pp. 909 - 915
• Main Authors: Nunes, J, Naymark, M, Sauer, L, Muhammad, A, Keun, H, Sturge, J, Stebbing, J, Waxman, J, Pchejetski, D
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 28.02.2012
• Subjects: Anemia; Angiogenesis; Antigens; Biomarkers; Biomarkers, Tumor - blood; Cancer research; Cardiovascular disease; Cell growth; Cell Line, Tumor; Disease Progression; Early Detection of Cancer - methods; Erythrocytes - metabolism; Humans; Hyperplasia; Kinases; Lysophospholipids - blood; Male; Medical research; Metastasis; Molecular Diagnostics; Mortality; Phosphotransferases (Alcohol Group Acceptor) - blood; Plasma; Prognosis; Prostate cancer; Prostate-Specific Antigen - blood; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - mortality; Proteins; Sphingosine - analogs & derivatives; Sphingosine - blood; United Kingdom > UK; United States > US
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2012.14

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, 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. 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.