You are prohibited from using or uploading content you accessed through this website into external applications, bots, software, or websites, including those using artificial intelligence technologies and infrastructure, including deep learning, machine learning and large language models and generative AI.
No AccessJournal of UrologyInvestigative Urology1 Apr 2014

Prostate Cancer Biomarker Profiles in Urinary Sediments and Exosomes

    View All Author Information


    Urinary biomarker tests for diagnosing prostate cancer have gained considerable interest. Urine is a complex mixture that can be subfractionated. We evaluated 2 urinary fractions that contain nucleic acids, ie cell pellets and exosomes. The influence of digital rectal examination before urine collection was also studied and the prostate cancer specific biomarkers PCA3 and TMPRSS2-ERG were assayed.

    Materials and Methods:

    Urine samples were prospectively obtained before and after digital rectal examination from 30 men scheduled for prostate biopsy. Cell pellet and exosomes were isolated and used for biomarker analysis. Analytical and diagnostic performance was tested using the Student t-test and ROC curves.


    Unlike the exosome fraction, urinary sediment gene expression analysis was compromised by amorphous precipitation in 10% of all specimens. Digital rectal examination resulted in increased mRNA levels in each fraction. This was particularly relevant for the exosomal fraction since after digital rectal examination the number of samples decreased in which cancer specific markers were below the analytical detection limit. Biomarker diagnostic performance was comparable to that in large clinical studies. In exosomes the biomarkers had to be normalized for prostate specific antigen mRNA while cell pellet absolute PCA3 levels had diagnostic value.


    Exosomes have characteristics that enable them to serve as a stable substrate for biomarker analysis. Thus, digital rectal examination enhances the analytical performance of biomarker analysis in exosomes and cell pellets. The diagnostic performance of biomarkers in exosomes differs from that of cell pellets. Clinical usefulness must be prospectively assessed in larger clinical cohorts.


    • 1 : Global cancer statistics. CA Cancer J Clin2011; 61: 69. Google Scholar
    • 2 : DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. Cancer Res1999; 59: 5975. Google Scholar
    • 3 : Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science2005; 310: 644. Google Scholar
    • 4 : Prevalence of TMPRSS2-ERG fusion prostate cancer among men undergoing prostate biopsy in the United States. Clin Cancer Res2009; 15: 4706. Google Scholar
    • 5 : Exosomal secretion of cytoplasmic prostate cancer xenograft-derived proteins. Mol Cell Proteomics2009; 8: 1192. Google Scholar
    • 6 : Mass spectrometric identification of human prostate cancer-derived proteins in serum of xenograft-bearing mice. Mol Cell Proteomics2006; 5: 1830. Google Scholar
    • 7 : Can urinary exosomes act as treatment response markers in prostate cancer?. J Transl Med2009; 7: 4. Google Scholar
    • 8 : Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer. Br J Cancer2009; 100: 1603. Google Scholar
    • 9 : Exosomes as biomarker treasure chests for prostate cancer. Eur Urol2011; 59: 823. Google Scholar
    • 10 : An analysis of urinary prostate specific antigen before and after radical prostatectomy: evidence for secretion of prostate specific antigen by the periurethral glands. J Urol1993; 149: 783. LinkGoogle Scholar
    • 11 : Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy. Eur Urol2008; 54: 1081. Google Scholar
    • 12 : APTIMA PCA3 molecular urine test: development of a method to aid in the diagnosis of prostate cancer. Clin Chem2006; 52: 1089. Google Scholar
    • 13 : Nucleic acids within urinary exosomes/microvesicles are potential biomarkers for renal disease. Kidney Int2010; 78: 191. Google Scholar
    • 14 Leyten GH, Hessels D, Jannink SA et al: Prospective multicentre evaluation of PCA3 and TMPRSS2-ERG gene fusions as diagnostic and prognostic urinary biomarkers for prostate cancer. Eur Urol 2012. Epub ahead of print. Google Scholar
    • 15 : Isolation and characterization of RNA-containing exosomes. J Vis Exp2012; 59: e3037. Google Scholar
    • 16 : Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci U S A2004; 101: 13368. Google Scholar
    • 17 : The time-resolved fluorescence-based PCA3 test on urinary sediments after digital rectal examination; a Dutch multicenter validation of the diagnostic performance. Clin Cancer Res2007; 13: 939. Google Scholar
    • 18 : DD3(PCA3)-based molecular urine analysis for the diagnosis of prostate cancer. Eur Urol2003; 44: 8. Google Scholar
    • 19 : Predictive value of PCA3 in urinary sediments in determining clinico-pathological characteristics of prostate cancer. Prostate2010; 70: 10. Google Scholar