SERUM SARCOSINE INCREASES THE ACCURACY OF PROSTATE CANCER DETECTION IN LOW RANGE PSA

Introduction & Objectives: High-throughput analysis of low-molecular-weight metabolites, represents a new tool for the global assessment of a cellular state, taking into account genetic regulation, altered kinetic activity of enzymes, and changes in metabolic reactions and regulation. Recently, sarcosine, an N-methyl derivative of glycine, was identified as a differential metabolite highly increased during prostate cancer (PCa) progression. In the present study we assessed the utility of sarcosine detected in serum as a biomarker for PCa and reported the association between the sarcosine levels and clinical-pathological parameters. Materials & Methods: In prospective fashion, sarcosine was measured in serum samples from subjects 289 PCa patients and 312 patients with no evidence of malignancy (NEM), confirmed by 8–12 core prostate biopsies. Sarcosine was measured using the Sarcosine Assay Kit (Biovision, Mountain View, CA, USA) following the manufacturer’s instructions. Nonparametric statistical tests and receiver operating characteristics (ROC) analyses were performed to assess the diagnostic performance. Results: According to A. Sreekumar et al. study, we initially restricted the analysis to patients with PSA values in the grey zone of 2-10 ng/ml, but we didn’t find a better diagnostic performance of sarcosine (AUC=0.57; 95% CI: 0.52, 0,62) vs total PSA (AUC=0.56; 95% CI: 0.51, 0,61) (p=0.7) and vs % fPSA. (AUC=0.68; 95% CI: 0.63, 0,73) (p=0.004). After we investigated the performance of sarcosine in other range of PSA (PSA<4 ng/ml; 410 ng/ml). ROC analysis on subjects with PSA<4 mg/l showed a higher predictive value of sarcosine vs total PSA (sarcosine AUC= 0.668; 95% CI: 0.58 to 0,74 vs total PSA AUC=0,53; 95% CI: 0.45 to 0,62) (p=0.039). ROC analyses for the other two ranges of PSA, showed the predictive superiority of %PSA vs sarcosine. Sarcosine values were not associated with tumour stage (pT2 vs pT3) or grade (Gleason score <7 vs ≥7). Conclusions: We reported the first independent study to validate the role of serum sarcosine in the diagnosis of prostate cancer. We provided evidence that serum sarcosine had a higher predictive value than tPSA and % fPSA in patients with PSA<4 ng/ml. Moreover serum sarcosine was not associated with tumor stage and grade, weakening its possible role in predicting cancer aggressiveness, as initially postulated