Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter September 30, 2014

Urinary thiosulfate as failed prostate cancer biomarker – an exemplary multicenter re-evaluation study

  • Carsten Stephan , Jacek Wilkosz , Waldemar Różański , Thorsten H. Ecke , Michael Lein , Magdalena Bryś , Anna Krześlak , Grażyna Chwatko and Klaus Jung EMAIL logo

Abstract

Background: In 2013, thiosulfate in urine has been proposed as promising prostate cancer (PCa) biomarker. However, a missing comparison with other proven PCa markers suggested a re-evaluation study. Therefore, together with the authors from the initial study, the diagnostic accuracy of thiosulfate was compared with that of urinary prostate cancer associated 3 (PCA3), serum prostate health index (Phi), and percent free prostate-specific antigen (%fPSA). Thiosulfate was further measured in a multicenter approach to exclude center-related biases.

Methods: Thiosulfate, calculated as ratio of thiosulfate to urinary creatinine (TS/Crea ratio), was measured in two cohorts in a total of 269 patients. In the retrospective study (n=160) PCA3, Phi, PSA, and %fPSA were compared with the TS/Crea ratio between patients with and without PCa according to the prostate needle biopsy results. The second prospective cohort included 109 patients from four centers.

Results: The median TS/Crea ratio was not statistically different between the patients with and without PCa. The receiver-operating characteristics showed that the TS/Crea ratio was unable to discriminate between patients with and without PCa in contrast to %fPSA, Phi, and PCA3. In all four centers, the low median TS/Crea ratios (<1 mmol/mol) in both patient cohorts were confirmed and thiosulfate was again not able to distinguish between them (p-values, 0.13–0.90).

Conclusions: This study could not confirm the previously observed high median TS/Crea ratio in PCa patients in comparison to non-PCa patients. Thiosulfate subsequently failed as PCa biomarker while PCA3 and Phi showed the expected diagnostic improvement.


Corresponding author: Klaus Jung, Department of Urology, University Hospital Charité and Berlin Institute for Urologic Research, Schumannstrasse 20/21, 10117 Berlin, Germany, Phone: +49 30 450 515041, E-mail:
aCarsten Stephan, Jacek Wilkosz, Waldemar Różański, Grażyna Chwatko and Klaus Jung shared first and senior authorship, respectively.

References

1. Antenor JA, Han M, Roehl KA, Nadler RB, Catalona WJ. Relationship between initial prostate specific antigen level and subsequent prostate cancer detection in a longitudinal screening study. J Urol 2004;172:90–3.10.1097/01.ju.0000132133.10470.bbSearch in Google Scholar PubMed

2. 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 < or =4.0 ng per milliliter. N Engl J Med 2004;350:2239–46.10.1056/NEJMoa031918Search in Google Scholar PubMed

3. Postma R, Schroder FH, van Leenders GJ, Hoedemaeker RF, Vis AN, Roobol MJ, et al. Cancer detection and cancer characteristics in the European Randomized Study of Screening for Prostate Cancer (ERSPC) – Section Rotterdam. A comparison of two rounds of screening. Eur Urol 2007;52:89–97.10.1016/j.eururo.2007.01.030Search in Google Scholar PubMed

4. Stephan C, Ralla B, Jung K. Prostate-specific antigen and other serum and urine markers in prostate cancer. Biochim Biophys Acta 2014;1846:99–112.10.1016/j.bbcan.2014.04.001Search in Google Scholar PubMed

5. Filella X, Gimenez N. Evaluation of [-2]proPSA and prostate health index (phi) for the detection of prostate cancer: a systematic review and meta-analysis. Clin Chem Lab Med 2013;51: 729–39.10.1515/cclm-2012-0410Search in Google Scholar PubMed

6. Filella X, Foj L, Mila M, Auge JM, Molina R, Jimenez W. PCA3 in the detection and management of early prostate cancer. Tumour Biol 2013;34:1337–47.10.1007/s13277-013-0739-6Search in Google Scholar PubMed

7. Ioannidis JP. Biomarker failures. Clin Chem 2013;59:202–4.10.1373/clinchem.2012.185801Search in Google Scholar PubMed

8. Romero Otero J, Garcia Gomez B, Campos Juanatey F, Touijer KA. Prostate cancer biomarkers: an update. Urol Oncol 2014;32:252–60.10.1016/j.urolonc.2013.09.017Search in Google Scholar PubMed

9. Chwatko G, Forma E, Wilkocz J, Glowacki R, Jozwiak P, Rozanski W, et al. Thiosulfate in urine as a facilitator in the diagnosis of prostate cancer for patients with prostate-specific antigen less or equal 10 ng/ml. Clin Chem Lab Med 2013;51:1825–31.10.1515/cclm-2013-0069Search in Google Scholar PubMed

10. Predmore BL, Lefer DJ, Gojon G. Hydrogen sulfide in biochemistry and medicine. Antioxid Redox Signal 2012;17:119–40.10.1089/ars.2012.4612Search in Google Scholar PubMed PubMed Central

11. Jung K, Stephan C. Thiosulfate in urine: new hope or new failure of a biomarker for prostate cancer? Clin Chem Lab Med 2013;51:1695–7.10.1515/cclm-2013-0540Search in Google Scholar PubMed

12. Stephan C, Jung K, Semjonow A, Schulze-Forster K, Cammann H, Hu X, et al. Comparative assessment of urinary prostate cancer antigen 3 and TMPRSS2:ERG gene fusion with the serum [-2]proprostate-specific antigen-based prostate health index for detection of prostate cancer. Clin Chem 2013;59:280–8.10.1373/clinchem.2012.195560Search in Google Scholar PubMed

13. Groskopf J, Aubin SM, Deras IL, Blase A, Bodrug S, Clark C, et al. APTIMA PCA3 molecular urine test: development of a method to aid in the diagnosis of prostate cancer. Clin Chem 2006;52:1089–95.10.1373/clinchem.2005.063289Search in Google Scholar PubMed

14. Jung K, v.Klinggräff P, Brux B, Sinha P, Schnorr D, Loening SA. Preanalytical determinants of total and free prostate-specific antigen and their ratio: blood collection and storage conditions. Clin Chem 1998;44:685–8.10.1093/clinchem/44.3.685Search in Google Scholar

15. Semjonow A, Kopke T, Eltze E, Pepping-Schefers B, Burgel H, Darte C. Pre-analytical in-vitro stability of [-2]proPSA in blood and serum. Clin Biochem 2010;43:926–8.10.1016/j.clinbiochem.2010.04.062Search in Google Scholar PubMed

16. 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

17. Stephan C, Vincendeau S, Houlgatte A, Cammann H, Jung K, Semjonow A. Multicenter evaluation of [-2]proprostate-specific antigen and the prostate health index for detecting prostate cancer. Clin Chem 2013;59:306–14.10.1373/clinchem.2012.195784Search in Google Scholar PubMed

18. Passing H, Bablok W. A new biometrical procedure for testing the equality of measurements from two different analytical methods. Application of linear regression procedures for method comparison studies in clinical chemistry, Part I. J Clin Chem Clin Biochem 1983;21:709–20.Search in Google Scholar

19. DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988;44:837–45.10.2307/2531595Search in Google Scholar

20. Kattan MW. Factors affecting the accuracy of prediction models limit the comparison of rival prediction models when applied to separate data sets. Eur Urol 2011;59:566–7.10.1016/j.eururo.2010.11.039Search in Google Scholar PubMed

21. Durant W, 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

22. Durand M, Scott BJ. Geothermal ground gas emissions and indoor air pollution in Rotorua, New Zealand. Sci Total Environ 2005;345:69–80.10.1016/j.scitotenv.2004.10.023Search in Google Scholar PubMed

23. 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 PubMed

24. Florin TH, Neale G, Goretski S, Cummings JH. The sulfate content of foods and beverages. J Food Comp Anal 1993;6:140–51.10.1006/jfca.1993.1016Search in Google Scholar

25. Voroteliak V, Cowley DM, Florin TH. Improved colorimetric determination of urinary thiosulfate to study intermediate sulfur metabolism in humans. Clin Chem 1993;39:2533–4.10.1093/clinchem/39.12.2533Search in Google Scholar

26. Zhao K, Li S, Wu L, Lai C, Yang G. Hydrogen sulfide represses androgen receptor transactivation by targeting at the second zinc-finger module. J Biol Chem 2014;289:20824–35.10.1074/jbc.M114.559518Search in Google Scholar PubMed PubMed Central

27. Guo H, Gai JW, Wang Y, Jin HF, Du JB, Jin J. Characterization of hydrogen sulfide and its synthases, cystathionine beta-synthase and cystathionine gamma-lyase, in human prostatic tissue and cells. Urology 2012;79:483–5.10.1016/j.urology.2011.10.013Search in Google Scholar PubMed

Received: 2014-7-15
Accepted: 2014-9-2
Published Online: 2014-9-30
Published in Print: 2015-2-1

©2015 by De Gruyter

Downloaded on 16.5.2024 from https://www.degruyter.com/document/doi/10.1515/cclm-2014-0729/html
Scroll to top button