Thiosulfate in urine as a facilitator in the diagnosis of prostate cancer for patients with prostate-specific antigen less or equal 10 ng/mL
-
Grażyna Chwatko
, Ewa Forma
Abstract
Background: The aim of this study was to examine the level of thiosulfate in the urine of prostate cancer (PCa) patients and evaluate its usefulness in the diagnosis and monitoring of prostate malignant transformation. Thiosulfate is a naturally occurring product of hydrogen sulfide (H2S) metabolism. H2S is involved in many physiological and pathological processes including inflammation and tumorigenesis.
Methods: The determination of thiosulfate in the urine of PCa patients and healthy controls was performed by reverse-phased liquid chromatography using 2-chloro-1-methylquinolinium tetrafluoroborate as a derivatization reagent. Thiosulfate concentrations were normalized to urinary creatinine levels to compensate for variable diuresis.
Results: In the urine samples of PCa patients, the mean thiosulfate level was almost 50 times higher than in the control groups and five times higher than in the benign prostatic hyperplasia group. The level of thiosulfate did not correlate with the serum prostate-specific antigen (PSA) level or PSA density. Neither tumor stage nor tumor grade was associated with thiosulfate level.
Conclusions: The results suggest that thiosulfate concentration in urine may be a good facilitator in the diagnostics of PCa. The predictive accuracy of this method is particularly valuable for the diagnosis of patients with low serum PSA level and negative digital rectal examination and transrectal ultrasound results.
References
1. Roobol MJ, Haese A, Bjartell A. Tumour markers in prostate cancer III: biomarkers in urine. Acta Oncol 2011;50(Suppl 1):85–9.10.3109/0284186X.2010.524935Search in Google Scholar PubMed
2. Strope SA, Andriole GL. Prostate cancer screening: current status and future perspectives. Nat Rev Urol 2010;7:487–93.10.1038/nrurol.2010.120Search in Google Scholar PubMed
3. Berretta R, Moscato P. Cancer biomarker discovery: the entropic hallmark. PLoS One 2010;18:e12262.10.1371/journal.pone.0012262Search in Google Scholar PubMed PubMed Central
4. Couzin J. Biomarkers. Metabolite in urine may point to high-risk prostate cancer. Science 2009;323:865.10.1126/science.323.5916.865aSearch in Google Scholar PubMed
5. Durand M, Weinstein P. Thiosulfate in human urine following minor exposure to hydrogen sulfide: implications for forensic analysis of poisoning. Forensic Toxicol 2007;25:92–5.10.1007/s11419-007-0033-7Search in Google Scholar
6. Kage S, Takekawa K, Kurosaki K, Imamura T, Kudo K. The usefulness of thiosulfate as an indicator of hydrogen sulfide poisoning: three cases. Int J Legal Med 1997;110:220–2.10.1007/s004140050071Search in Google Scholar PubMed
7. Lavu M, Bhushan S, Lefer, DJ. Hydrogen sulfide-mediated cardioprotection: mechanisms and therapeutic potential. Clin Sci 2010;120:219–29.10.1042/CS20100462Search in Google Scholar PubMed
8. Whiteman M, Moore PK. Hydrogen sulfide and the vasculature: a novel vasculoprotective entity and regulator of nitric oxide bioavailability? J Cell Mol Med 2009;13:488–507.10.1111/j.1582-4934.2009.00645.xSearch in Google Scholar PubMed PubMed Central
9. Whiteman M, Winyard PG. Hydrogen sulfide and inflammation: the good, the bad, the ugly and the promising. Expert Rev Clin Pharmacol 2011;4:13–32.10.1586/ecp.10.134Search in Google Scholar PubMed
10. Gong QH, Shi XR, Hong ZY, Pan LL, Liu XH, Zhu YZ. A new hope for neurodegeneration: possible role of hydrogen sulfide. J Alzheimers Dis 2011;24:173–82.10.3233/JAD-2011-110128Search in Google Scholar PubMed
11. Whiteman M, Gooding KM, Whatmore JL, Ball CI, Mawson D, Skinner K, et al. Adiposity is a major determinant of plasma levels of the novel vasodilator hydrogen sulphide. Diabetologia 2010;53:1722–6.10.1007/s00125-010-1761-5Search in Google Scholar
12. Cole DE, Evrovski J. Screening for sulfite oxidase deficiency with urinary thiosulfate/sulfate ratios determined by anion chromatography. Clin Chem 1996;42:654–5.10.1093/clinchem/42.4.654Search in Google Scholar
13. Belardinelli MC, Chabli A, Chadefaux-Vekemans B, Kamoun P. Urinary sulfur compounds in Down syndrome. Clin Chem 2001;47:1500–1.10.1093/clinchem/47.8.1500Search in Google Scholar
14. Torun M, Bayhan A, Yentür G. Response of allergic and normal persons to sulfiting agents in wine: determination of thiosulfate excretion in urine. Clin Chem 1989;35:1792–3.10.1093/clinchem/35.8.1792Search in Google Scholar
15. Baskar R, Bian J. Hydrogen sulfide gas has cell growth regulatory role. Eur J Pharmacol 2011;656:5–9.10.1016/j.ejphar.2011.01.052Search in Google Scholar
16. Deras IL, Aubin SM, Blase A, Day JR, Koo S, Partin AW, et al. PCA3: a molecular urine assay for predicting prostate biopsy outcome. J Urol 2008;179:1587–92.10.1016/j.juro.2007.11.038Search in Google Scholar
17. Chwatko G, Bald E. Determination of thiosulfate in human urine by high performance liquid chromatography. Talanta 2009;79:229–34.10.1016/j.talanta.2009.03.040Search in Google Scholar
18. Shi H, Ma Y, Ma Y. A simple and fast method to determine and quantify urinary creatinine. Anal Chim Acta 1995;312:79–83.10.1016/0003-2670(95)00208-HSearch in Google Scholar
19. Jung K. Enzyme activities in urine: how should we express their excretion? A critical literature review. Eur J Clin Chem Clin Biochem 1991;29:725–9.Search in Google Scholar
20. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, et al. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature 2009;457:910–4.10.1038/nature07762Search in Google Scholar PubMed PubMed Central
21. Cai WJ, Wang MJ, Ju LH, Wang C, Zhu YC. Hydrogen sulfide induces human colon cancer cell proliferation: role of Akt, ERK and p21. Cell Biol Int 2010;34:565–72.10.1042/CBI20090368Search in Google Scholar PubMed
22. Cao Q, Zhang L, Yang G, Xu C, Wang R. Butyrate-stimulated H2S production in colon cancer cells. Antioxi Redox Signal 2010;12:1101–9.10.1089/ars.2009.2915Search in Google Scholar
23. Guo H, Gai JW, Wang Y, Jin HF, Du JB, Jin J. Characterization of hydrogen sulfide and its synthases, cystathionine β-synthase and cystathionine γ-lyase, in human prostatic tissue and cells. Urology 2012;79:483.e1–5.10.1016/j.urology.2011.10.013Search in Google Scholar
24. Łowicka E. Bełtowski J. Hydrogen sulfide (H2S) – the third gas of interest for pharmacologists. Pharmacol Rep 2007;59:4–24.Search in Google Scholar
25. Ramasamy S, Singh S, Taniere P, Langman MJ, Eggo MC. Sulfide-detoxifying enzymes in human colon are decreased in cancer and upregulated in differentiation. Am J Physiol Gastroinvest 2006;191:288–96.10.1152/ajpgi.00324.2005Search in Google Scholar
26. Lee F, Torp-Pedersen S, Littrup PJ, McLeary RD, McHugh TA, Smid AP, et al. Hypoechoic lesions of the prostate: clinical relevance of tumor size, digital rectal examination, and prostate-specific antigen. Radiology 1989;170:29–32.10.1148/radiology.170.1.2462262Search in Google Scholar
27. Crawford ED, Leewansangtong S, Goktas S, Holthaus K, Baier M. Efficiency of prostate-specific antigen and digital rectal examination in screening, using 4.0 ng/mL and age-specific reference range as a cut-off for abnormal values. Prostate 1999;3841:296–302.10.1002/(SICI)1097-0045(19990301)38:4<296::AID-PROS5>3.0.CO;2-PSearch in Google Scholar
28. Catalona WJ, Richie JP, Ahmann FR, Hudson MA, Scardio PT, Flanigan RC, et al. Comparison of digital rectal examination and serum prostate specific antigen in the early detection of prostate cancer: results of a multicenter clinical trial of 6,630 men. J Urol 1994;151:1283–90.10.1016/S0022-5347(17)35233-3Search in Google Scholar
29. Benson MC, Whang IS, Olsson CA, McMahon DJ, Cooner WH. The use of prostate specific antigen density to enhance the predictive value of intermediate levels of serum prostate specific antigen. J Urol 1992;147:817–21.10.1016/S0022-5347(17)37394-9Search in Google Scholar
30. Ciatto S, Bonardi R, Mazzotta A, Lombardi C, Santoni R, Cardini S, et al. Comparing two modalities of screening for prostate cancer: digital rectal examination+transrectal ultrasonography vs. prostate-specific antigen. Tumori 1995;81:225–9.10.1177/030089169508100401Search in Google Scholar
31. Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL, et al. Prevalence of prostate cancer among men with a prostate-specific antigen level ≤4.0 ng per milliliter. N Engl J Med 2004;350:2239–46.10.1056/NEJMoa031918Search in Google Scholar
©2013 by Walter de Gruyter Berlin Boston
Articles in the same Issue
- Masthead
- Masthead
- Editorials
- What is a biomarker? It’s time for a renewed definition
- Biomarker research and leading causes of death worldwide: a rather feeble relationship
- Thiosulfate in urine: new hope or new failure of a biomarker for prostate cancer?
- Review
- Acute coronary syndrome – the present and future role of biomarkers1)
- Mini Review
- Advance in molecular diagnostic tools for hepatitis B virus detection
- Opinion Paper
- Standardization and analytical goals for glycated hemoglobin measurement
- Guidelines and Recommendations
- Proposal for the use in emergency departments of cardiac troponins measured with the latest generation methods in patients with suspected acute coronary syndrome without persistent ST-segment elevation
- General Clinical Chemistry and Laboratory Medicine
- Current status of verification practices in clinical biochemistry in Spain
- Two site evaluation of the performance of a new generation point-of-care glucose meter for use in a neonatal intensive care unit
- Trp64Arg (rs4994) polymorphism of β3-adrenergic receptor gene is associated with hyperuricemia in a Chinese male population
- Quantification of vancomycin in human serum by LC-MS/MS
- Automated indirect immunofluorescence antinuclear antibody analysis is a standardized alternative for visual microscope interpretation
- Autocorrelation and cross-correlation between hCGβ and PAPP-A in repeated sampling during first trimester of pregnancy
- Platelet oxidative stress and systemic inflammation in chronic spontaneous urticaria
- Reference Values
- Establishment of reference values for novel urinary biomarkers for renal damage in the healthy population: are age and gender an issue?
- Risks of mortality associated with common laboratory tests: a novel, simple and meaningful way to set decision limits from data available in the Electronic Medical Record
- Cancer Diagnostics
- Cancer antigen 125, human epididymis 4, kallikrein 6, osteopontin and soluble mesothelin-related peptide immunocomplexed with immunoglobulin M in epithelial ovarian cancer diagnosis
- Thiosulfate in urine as a facilitator in the diagnosis of prostate cancer for patients with prostate-specific antigen less or equal 10 ng/mL
- Anemia and iron biomarkers in patients with early breast cancer. Diagnostic value of hepcidin and soluble transferrin receptor quantification1)
- Sensitive detection of EML4-ALK fusion oncoprotein of lung cancer by in situ proximity ligation assay
- Re-evaluation of laboratory predictors of response to current anemia treatment regimens of erythropoiesis stimulating agents in cancer patients
- Cardiovascular Diseases
- Evaluation of four sensitive troponin assays for risk assessment in acute coronary syndromes using a new clinically oriented approach for comparison of assays
- A combined index of cardiac biomarkers as a risk factor for early cardiovascular mortality in hemodialysis patients
- Prognostic utility of biochemical markers of cardiovascular risk: impact of biological variability
- Letters to the Editors
- Exploring the relationship between serum biomarkers, acute intracerebral changes and outcome after severe traumatic brain injury (TBI)
- Laboratory false-positive results: a clinician responsibility or a shared responsibility with requesting clinicians?
- The one hour lactose tolerance test
- High concentration of IgM-κ paraprotein causes over-estimation of serum total protein by certain biuret method
- Determining calculated free testosterone reference intervals in a normal adult male population
- Alveolar neopterin, procalcitonin, and IL-6 in relation to serum levels and severity of lung injury in ARDS
- Falsely elevated cobalamin concentration in multiple assays in a patient with pernicious anemia: a case study
- Leading Figures in Laboratory Medicine
- Research forever – Klaus Jung
Articles in the same Issue
- Masthead
- Masthead
- Editorials
- What is a biomarker? It’s time for a renewed definition
- Biomarker research and leading causes of death worldwide: a rather feeble relationship
- Thiosulfate in urine: new hope or new failure of a biomarker for prostate cancer?
- Review
- Acute coronary syndrome – the present and future role of biomarkers1)
- Mini Review
- Advance in molecular diagnostic tools for hepatitis B virus detection
- Opinion Paper
- Standardization and analytical goals for glycated hemoglobin measurement
- Guidelines and Recommendations
- Proposal for the use in emergency departments of cardiac troponins measured with the latest generation methods in patients with suspected acute coronary syndrome without persistent ST-segment elevation
- General Clinical Chemistry and Laboratory Medicine
- Current status of verification practices in clinical biochemistry in Spain
- Two site evaluation of the performance of a new generation point-of-care glucose meter for use in a neonatal intensive care unit
- Trp64Arg (rs4994) polymorphism of β3-adrenergic receptor gene is associated with hyperuricemia in a Chinese male population
- Quantification of vancomycin in human serum by LC-MS/MS
- Automated indirect immunofluorescence antinuclear antibody analysis is a standardized alternative for visual microscope interpretation
- Autocorrelation and cross-correlation between hCGβ and PAPP-A in repeated sampling during first trimester of pregnancy
- Platelet oxidative stress and systemic inflammation in chronic spontaneous urticaria
- Reference Values
- Establishment of reference values for novel urinary biomarkers for renal damage in the healthy population: are age and gender an issue?
- Risks of mortality associated with common laboratory tests: a novel, simple and meaningful way to set decision limits from data available in the Electronic Medical Record
- Cancer Diagnostics
- Cancer antigen 125, human epididymis 4, kallikrein 6, osteopontin and soluble mesothelin-related peptide immunocomplexed with immunoglobulin M in epithelial ovarian cancer diagnosis
- Thiosulfate in urine as a facilitator in the diagnosis of prostate cancer for patients with prostate-specific antigen less or equal 10 ng/mL
- Anemia and iron biomarkers in patients with early breast cancer. Diagnostic value of hepcidin and soluble transferrin receptor quantification1)
- Sensitive detection of EML4-ALK fusion oncoprotein of lung cancer by in situ proximity ligation assay
- Re-evaluation of laboratory predictors of response to current anemia treatment regimens of erythropoiesis stimulating agents in cancer patients
- Cardiovascular Diseases
- Evaluation of four sensitive troponin assays for risk assessment in acute coronary syndromes using a new clinically oriented approach for comparison of assays
- A combined index of cardiac biomarkers as a risk factor for early cardiovascular mortality in hemodialysis patients
- Prognostic utility of biochemical markers of cardiovascular risk: impact of biological variability
- Letters to the Editors
- Exploring the relationship between serum biomarkers, acute intracerebral changes and outcome after severe traumatic brain injury (TBI)
- Laboratory false-positive results: a clinician responsibility or a shared responsibility with requesting clinicians?
- The one hour lactose tolerance test
- High concentration of IgM-κ paraprotein causes over-estimation of serum total protein by certain biuret method
- Determining calculated free testosterone reference intervals in a normal adult male population
- Alveolar neopterin, procalcitonin, and IL-6 in relation to serum levels and severity of lung injury in ARDS
- Falsely elevated cobalamin concentration in multiple assays in a patient with pernicious anemia: a case study
- Leading Figures in Laboratory Medicine
- Research forever – Klaus Jung