Circulating sphingosine-1-phosphate and erythrocyte sphingosine kinase-1 activity as novel biomarkers for early prostate cancer detection.
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) (n=110) 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.


CONCLUSIONS
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.
Department of Surgery and Cancer, Imperial College London, Cyclotron Building, Ducane Road, London W12 0NN, UK.
J
J
Nunes
M
M
Naymark
L
L
Sauer
A
A
Muhammad
H
H
Keun
J
J
Sturge
J
J
Stebbing
J
J
Waxman
D
D
Pchejetski
D000740:Anemia; D014408:Biomarkers, Tumor / Q000097:blood; D045744:Cell Line, Tumor; D018450:Disease Progression; D055088:Early Detection of Cancer / Q000379:methods; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D008246:Lysophospholipids / Q000097:blood*; D008297:Male; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000097:blood*; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood; D000099157:Sphingosine Kinase
D014408:Biomarkers, Tumor; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D017430:Prostate-Specific Antigen; D013110:Sphingosine; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate