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

L Bohm, A M Serafin, P Fernandez, G Van der Watt, P J D Bouic, J Harvey
2012 South African Medical Journal  
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
more » ... ostate 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. Methods Patient 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 into an Agilent 7890A/5975C GCMS system fitted with a Zebron ZB AAA 10 m x 0.25 mm capillary GC column. The sample
doi:10.7196/samj.5768 fatcat:dlnt5hiqgngptlh75urykd2ibu