Plasma sarcosine does not distinguish early and advanced stages of prostate cancer

Abstract

The identification of prostate cancer remains problematic; no single, simple procedure exists for a reliable diagnosis. Prostate specific antigen (PSA), while non-invasive and easily measurable in serum, is not specific owing to false-positives from benign prostatic hyperplasia (BPH), inflammatory conditions and prostatic trauma. Additional diagnostic information must therefore be obtained by transrectal ultrasonography (TRUS) and digital rectal examination (DRE) to assess prostate size and morphology. Final confirmation of a malignancy requires histopathological analysis of several biopsies. A remaining hurdle in the identification process is the existence of indolent organ-confined disease and aggressive metastatic prostate cancer that can only be distinguished by additional imaging or nuclear medicine procedures.In a new approach to this diagnostic dilemma, it has been argued that screening for changes in metabolite expression resulting from gene silencing and gene activation could be used to identify a specific biological marker that increases in the transformation process. Therefore, a paper elaborating on metabolite expression in clinical samples of benign, localised and metastatic prostate cancer 1 was enthusiastically received and debated in editorials. [2][3][4][5] The proposal that sarcosine (N-methylglycine) (a metabolite of choline found in urine) may be characteristic for prostate cancer progression has since been examined in other laboratories. 1 These investigations found sarcosine levels in urine 6 and serum 7 to be constant, irrespective of sample pathology. From our own and published preliminary measurements, it is nevertheless clear that sarcosine-alanine ratios in prostate tumour patients are often elevated above controls and are spread over a wider range. 1,7,17 A relationship between sarcosine and disease therefore cannot as yet be totally ruled out. Interest in sarcosine as a marker molecule remains topical, as shown by a recent modification of sarcosine assay by GC/MS in urine. 8 We present measurements in plasma of prostate cancer patients characterised by PSA, tumour stage and Gleason score using GC/MS for sarcosine methodology 9,10 to elaborate further on the suitability of sarcosine as a marker for prostate cancer. MethodsPatient blood was collected by venipuncture and centrifuged, and clear supernatants were stored at -20°C. The AxSYM total PSA was determined by a MEIA microparticle enzyme immune assay (Abbott) and expressed as ng/ml. Ethical approval was granted by the University of Stellenbosch Health Research Ethics Committee (N09/11/330).Sarcosine and alanine were quantified in plasma by gaschromatograph mass spectrometry. Briefly, amino acids were extracted from 100 µl of acidified plasma by solid phase extraction onto a cation exchange column before being washed, eluted and derivatised to their corresponding alkyl chloroformates using a commercial kit (EZ:faast, Phenomenex, Torrance CA, USA). After derivatisation, the amino acids were extracted into solvent and 2 µl injected in...

Application of Holistic Liquid Chromatography-High Resolution Mass Spectrometry Based Urinary Metabolomics for Prostate Cancer Detection and Biomarker Discovery

“…Some other features could also be considered as potential biomarkers because of significant statistical results although they were only present in a single LC-HRMS condition. The discriminative ability of sarcosine for prostate cancer was also evaluated (Table S1 in File S3); in keeping with several earlier reports, we found no significant difference in the sarcosine level between cancer and control groups [6], [8]–[10], [12], [15].…”

Sarcosine as a Potential Prostate Cancer Biomarker—A Review

“…It was therefore concluded that sarcosine is not a suitable marker for prostate cancer. By comparing PSA with T-stages in the same group of patients it was found that PSA in the T1–T2 group of patients was significantly lower than in the T3–T4 group of patients confirming the well know merits and limitations of this marker [61]. Reverse phase high performance liquid chromatography (HPLC) is the most utilized technique for separation of amino acids [62,63] or peptides [64].…”

“…In another published study gas chromatography (GC) and mass spectrometry (MS) were used. The results showed that the sarcosine/alanine ratios in patients with early and advanced prostate cancer were fairly constant showing no statistically significant differences between T-stages [61]. It was therefore concluded that sarcosine is not a suitable marker for prostate cancer.…”

A monolithic single-chip point-of-care platform for metabolomic prostate cancer detection

“…Finally, sarcosine has also been linked, albeit variably, to PCa for diagnosis 24 , malignancy assessment [23][24][25] , and staging 23,24,26,27 . While the evidence that sarcosine is a useful marker for PCa is debated 49,50 , we elected to add it to the present study. A more detailed review of metabolomics for PCa and our panel selection is provided in the Supplementary Information.…”