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Comparative analysis of prostate cancer specific biomarkers PCA3 and ERG in whole urine, urinary sediments and exosomes

  • Rianne J. Hendriks , Siebren Dijkstra , Sander A. Jannink , Martijn G. Steffens , Inge M. van Oort , Peter F.A. Mulders and Jack A. Schalken EMAIL logo
Published/Copyright: December 2, 2015
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 54 Issue 3

Abstract

Background:PCA3 and ERG are mRNA-based prostate cancer (PCa) specific biomarkers that can be detected in urine. However, urine is a complex substrate that can be separated in several fractions. In this study we compared the levels of PCa-specific biomarkers (PCA3 and ERG) and KLK3 as prostate-specific reference gene in three urine substrates–whole urine, urinary sediment (cell pellet) and exosomes–and evaluated the influence of performing a digital rectal examination (DRE) prior to urine sampling.

Methods: First-voided urine samples were prospectively obtained before and after DRE from 29 men undergoing prostate biopsies. The urine was separated in whole urine, cell pellet and exosomes and the biomarker levels were measured with RT-qPCR.

Results: PCa was identified in 52% (15/29) of men. In several samples the mRNA levels were below the analytical limit of detection (BDL). The biomarker levels were highest in whole urine and significantly higher after DRE in all substrates. In PCa patients higher levels of PCA3 and ERG were found in all urine substrates after DRE compared to non-PCa patients.

Conclusions: This is the first study in which urinary PCa-specific biomarker levels were compared directly in three separate urine fractions. These results suggest that whole urine could be the urine substrate of choice for PCa-diagnostics based on analytical sensitivity, which is reflected directly in the high informative rate. Moreover, the significant positive effect of performing a DRE prior to urine sampling is confirmed. These findings could be of influence in the development of PCa-diagnostic urine tests.

Keywords: biomarkers; exosomes; PCA3; prostate cancer; urine
Corresponding author: Prof. Dr. Jack A. Schalken, Department of Urology, Radboud University Medical Center, Geert-Grooteplein Zuid 10, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands, Phone: +31 24 36 14 146, E-mail: ; and Department of Research and Development, NovioGendix, Nijmegen, The Netherlands

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Supplemental Material:

The online version of this article (DOI: 10.1515/cclm-2015-0599) offers supplementary material, available to authorized users.

Received: 2015-6-25
Accepted: 2015-10-22
Published Online: 2015-12-2
Published in Print: 2016-3-1

©2016 by De Gruyter

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https://doi.org/10.1515/cclm-2015-0599
Keywords for this article
biomarkers; exosomes; PCA3; prostate cancer; urine

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. The way of prostate cancer diagnostics
  4. Review
  5. Statistical methods used in the calculation of geriatric reference intervals: a systematic review
  6. Opinion Paper
  7. The side effects of translational omics: overtesting, overdiagnosis, overtreatment
  8. Genetics and Molecular Diagnostics
  9. Rapid detection of non-deletional mutations causing α-thalassemia by multicolor melting curve analysis
  10. General Clinical Chemistry and Laboratory Medicine
  11. Patient pools and the use of “patient means” are valuable tools in quality control illustrated by a bone-specific alkaline phosphatase assay
  12. Long-term stability of glucose: 96-h study using Terumo Glycaemia tubes
  13. Glucose is stable during prolonged storage in un-centrifuged Greiner tubes with liquid citrate buffer, but not in serum and NaF/KOx tubes
  14. Croatian laboratories have a good knowledge of the proper detection and management of hemolyzed, icteric and lipemic samples
  15. Fetal exposure to ethanol: relationship between ethyl glucuronide in maternal hair during pregnancy and ethyl glucuronide in neonatal meconium
  16. Comparing the effect of isotopically labeled or structural analog internal standards on the performance of a LC-MS/MS method to determine ciclosporin A, everolimus, sirolimus and tacrolimus in whole blood
  17. Relationship between matrix metalloproteinase-9 and oxidative stress in drug-free male schizophrenia: a case control study
  18. Comparison of functional fibrinogen (FF/CFF) and FIBTEM in surgical patients – a retrospective study
  19. Reference Values and Biological Variations
  20. Assessment of serum free light chain levels in healthy adults immediately after marathon running
  21. Pharmacokinetics of a novel dosing regimen of oral melatonin in critically ill patients
  22. Cancer Diagnostics
  23. An epidemiology-based model as a tool to monitor the outbreak of inappropriateness in tumor marker requests: a national scale study
  24. Comparative analysis of prostate cancer specific biomarkers PCA3 and ERG in whole urine, urinary sediments and exosomes
  25. Infectious Diseases
  26. Comparative evaluation of the Aptima HIV-1 Quant Dx assay and COBAS TaqMan HIV-1 v2.0 assay using the Roche High Pure System for the quantification of HIV-1 RNA in plasma
  27. Evaluating the use of procalcitonin in an asymptomatic, HIV-infected antiretroviral therapy-naïve, South African cohort
  28. Diabetes
  29. Early prediction of gestational diabetes: a practical model combining clinical and biochemical markers
  30. Letters to the Editors
  31. Highly-trained dogs’ olfactory system for detecting biochemical recurrence following radical prostatectomy
  32. More on the accuracy of the Architect enzymatic assay for hemoglobin A1c and its traceability to the IFCC reference system
  33. Assessing quality from an accuracy-based HbA1c proficiency survey
  34. HbG-Honolulu interferes with some cation-exchange HPLC HbA1c assays
  35. Between analyser differences in chloride measurements and thus anion gap cause different interpretations of the acid-base balance
  36. Non-albumininuric proteinuria: a urinary tubular marker in the diagnosis of diabetic kidney disease
  37. International Normalized Ratio (INR) testing: analytical and clinical performance of four point-of-care devices versus central laboratory instrumentation analysis
  38. Genetic screening of the makorin ring finger 3 gene in girls with idiopathic central precocious puberty
  39. Practical approach for medical validation of therapeutic drug monitoring results
  40. Marked elevation of procalcitonin in a patient with a drug related infusion reaction to rituximab
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