Serum sarcosine is not a marker for prostate cancer

The recent finding by Sreekumar et al. ¹ that sarcosine might play a role in the progression of prostate cancer was warmly welcomed by professionals in the field. ² The assessment of sarosine concentration in body fluids was hypothesized to serve as a novel marker for prostate cancer and prostate cancer progression. ³ Currently, the blood concentration of prostate-specific antigen (PSA), a protein produced by the prostate gland, is used as a biological marker, with the limitation that an increased concentration of PSA alone does not differentiate between benign prostate conditions and prostate cancer. Sarcosine, also known as N-methylglycine, is a small endogenous molecule present in low concentrations in blood.

Careful interpretation of the data presented (Supplementary Figure 14) by Sreekumar et al. ¹ already showed a substantial overlap in the urinary sarcosine concentrations between men with positive and negative biopsies for cancer, implying that assessment of urinary sarcosine alone will not have clinical relevance on an individual basis. Potentially however, serum PSA concentrations in relation to serum sarcosine concentrations might have additional diagnostic value. We retrospectively determined serum sarcosine concentrations in samples obtained from three groups of men: controls (i.e. individuals who have been assessed for vitamin B₁₂ status [n = 15]), individuals with increased serum PSA (n = 24) and individuals with prostate cancer metastases (n = 18).

Sarcosine was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) using stable-isotope labelled [ ² H₃]sarcosine as internal standard. The LC-MS/MS method was evaluated with respect to linearity, recovery and reproducability. The structural analogues alanine and beta-alanine were physically separated from sarcosine by the LC column allowing proper quantification.

The outcomes of the sarcosine determinations are depicted in Figure 1. Our results clearly show that the mean serum sarcosine concentration does not discriminate between the three groups of men. Moreover, on an individual basis the sarcosine concentration was uninformative with respect to increased PSA concentrations and to prostate cancer progression. Our serum sarcosine data in conjunction with the urinary sarcosine data presented by Sreekumar and colleagues ¹ shows that there are no major alterations in the extracellular concentrations of sarcosine, implying that the assessment of sarcosine in easily obtainable body fluids like urine and serum has limited potential in the diagnostic algorithm of prostate cancer.

Figure 1

Comparison of serum sarcosine concentrations between the three groups depicted as box plots. Statistical evaluation of the data using the non-parametric Kruskal–Wallis test indicated that there are no statistical significant differences in the sarcosine concentrations between the three groups. Outliers are shown as open circles

DECLARATIONS

Competing interests: All authors declare that there are no actual or potential conflicts of interest including any financial, personal or other relationships with other people or organizations.

Guarantor: MAB.

Contributorship: EAS wrote manuscript, researched data, contributed to discussion; ACH researched data, contributed to discussion, reviewed/edited manuscript; JVM selected patients, contributed to discussion, reviewed/edited manuscript; CJ contributed to discussion, reviewed/edited manuscript; and MAB contributed to discussion, reviewed/edited manuscript.