Research Article

You have free access to this content

Discovery and validation of urinary biomarkers for prostate cancer

  1. Dan Theodorescu1,2,3,†,
  2. Eric Schiffer4,†,
  3. Hartwig W. Bauer5,
  4. Friedrich Douwes6,
  5. Frank Eichhorn7,
  6. Reinhard Polley8,
  7. Thomas Schmidt9,
  8. Wolfgang Schöfer10,
  9. Petra Zürbig4,
  10. David M. Good11,
  11. Joshua J. Coon11,12,
  12. Harald Mischak Dr.4,*

Article first published online: 7 MAR 2008

DOI: 10.1002/prca.200780082

Issue

PROTEOMICS - Clinical Applications

PROTEOMICS - Clinical Applications

Volume 2, Issue 4, pages 556–570, No. 4 April 2008

Additional Information

How to Cite

Theodorescu, D., Schiffer, E., Bauer, H. W., Douwes, F., Eichhorn, F., Polley, R., Schmidt, T., Schöfer, W., Zürbig, P., Good, D. M., Coon, J. J. and Mischak, H. (2008), Discovery and validation of urinary biomarkers for prostate cancer. Prot. Clin. Appl., 2: 556–570. doi: 10.1002/prca.200780082

Author Information

  1. 1

    Department of Urology, University of Virginia, Charlottesville, VA, USA

  2. 2

    Mellon Prostate Cancer Institute, University of Virginia, Charlottesville, VA, USA

  3. 3

    Department of Molecular Physiology, University of Virginia, Charlottesville, VA, USA

  4. 4

    Mosaiques Diagnostics and Therapeutics AG, Hannover, Germany

  5. 5

    Ludwig-Maximilian-University Munich, Munich, Germany

  6. 6

    St. George Hospital Bad Aibling, Bad Aibling, Germany

  7. 7

    Urological Office, Bad Reichenhall, Germany

  8. 8

    Urological Office, Urologie am Aegi, Hannover, Germany

  9. 9

    Urological Office, Brackenheim, Germany

  10. 10

    Urological Office, Höchstadt, Germany

  11. 11

    Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA

  12. 12

    Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI, USA

  1. †

    Both authors contributed equally.

*Mosaiques Diagnostics and Therapeutics AG, Mellendorfer Str. 7-9, 30625 Hannover, Germany Fax: +49-511-55474431

Publication History

  1. Issue published online: 3 APR 2008
  2. Article first published online: 7 MAR 2008
  3. Manuscript Received: 12 OCT 2007

Funded by

  • NIH. Grant Number: CA104106
  • Eurotransbio. Grant Number: ETB-2006-016
  • University of Wisconsin-Madison
  • Thermo Fisher
  • National Institutes of Health. Grant Number: 1R01GM080148
  • Biotechnology Training Program. Grant Number: NIH 5T32GM08349

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

Get PDF (528K)

References

  • 1
    Jemal, A., Siegel, R., Ward, E., Murray, T. et al., Cancer statistics, 2006. CA Cancer J. Clin. 2006, 56, 106–130.
    Direct Link:
  • 2
    Stamey, T. A., Yang, N., Hay, A. R., McNeal, J. E. et al., Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N. Engl. J. Med. 1987, 317, 909–916.
  • 3
    Presti, J. C., Jr., Prostate cancer: Assessment of risk using digital rectal examination, tumor grade, prostate-specific antigen, and systematic biopsy. Radiol. Clin. North Am. 2000, 38, 49–58.
  • 4
    Thompson, I. M., Goodman, P. J., Tangen, C. M., Lucia, M. S. et al., The influence of finasteride on the development of prostate cancer. N. Engl. J. Med. 2003, 349, 215–224.
  • 5
    Thompson, I. M., Pauler, D. K., Goodman, P. J., Tangen, C. M. 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, 2239–2246.
  • 6
    Wang, X., Yu, J., Sreekumar, A., Varambally, S. et al., Autoantibody signatures in prostate cancer. N. Engl. J. Med. 2005, 353, 1224–1235.
  • 7
    Ornstein, D. K., Rayford, W., Fusaro, V. A., Conrads, T. P. et al., Serum proteomic profiling can discriminate prostate cancer from benign prostates in men with total prostate specific antigen levels between 2.5 and 15.0 ng/ml. J. Urol. 2004, 172, 1302–1305.
  • 8
    Conrads, T. P., Hood, B. L., Issaq, H. J., Veenstra, T. D., Proteomic patterns as a diagnostic tool for early-stage cancer: A review of its progress to a clinically relevant tool. Mol. Diagn. 2004, 8, 77–85.
  • 9
    Gelmann, E. P., Semmes, O. J., Expression of genes and proteins specific for prostate cancer. J. Urol. 2004, 172, S23–S26.
  • 10
    Kolch, W., Neususs, C., Pelzing, M., Mischak, H., Capillary electrophoresis-mass spectrometry as a powerful tool in clinical diagnosis and biomarker discovery. Mass Spectrom. Rev. 2005, 24, 959–977.
    Direct Link:
  • 11
    Mueller, J., von Eggeling, F., Driesch, D., Schubert, J. et al., ProteinChip technology reveals distinctive protein expression profiles in the urine of bladder cancer patients. Eur. Urol. 2005, 47, 885–893.
  • 12
    Vlahou, A., Schellhammer, P. F., Mendrinos, S., Patel, K. et al., Development of a novel proteomic approach for the detection of transitional cell carcinoma of the bladder in urine. Am. J. Pathol. 2001, 158, 1491–1502.
  • 13
    Vlahou, A., Giannopoulos, A., Gregory, B. W., Manousakas, T. et al., Protein profiling in urine for the diagnosis of bladder cancer. Clin. Chem. 2004, 50, 1438–1441.
  • 14
    Munro, N. P., Cairns, D. A., Clarke, P., Rogers, M. et al., Urinary biomarker profiling in transitional cell carcinoma. Int. J. Cancer 2006, 119, 2642–2650.
    Direct Link:
  • 15
    Zhang, Y. F., Wu, D. L., Guan, M., Liu, W. W. et al., Tree analysis of mass spectral urine profiles discriminates transitional cell carcinoma of the bladder from noncancer patient. Clin. Biochem. 2004, 37, 772–779.
  • 16
    Liu, W., Guan, M., Wu, D., Zhang, Y. et al., Using tree analysis pattern and SELDI-TOF-MS to discriminate transitional cell carcinoma of the bladder cancer from noncancer patients. Eur. Urol. 2005, 47, 456–462.
  • 17
    Zerefos, P., Prados, J., Kossida, S., Kalousis, A., Vlahou, A., Sample preparation and bioinformatics in MALDI profiling of urinary proteins. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2007, 853, 20–30.
  • 18
    Kaiser, T., Wittke, S., Just, I., Krebs, R. et al., Capillary Electrophoresis coupled to mass spectrometer for automated and robust polypeptide determination in body fluids for clinical use. Electrophoresis 2004, 25, 2044–2055.
    Direct Link:
  • 19
    Theodorescu, D., Wittke, S., Ross, M. M., Walden, M. et al., Discovery and validation of new protein biomarkers for urothelial cancer: A prospective analysis. Lancet Oncol. 2006, 7, 230–240.
  • 20
    Schaub, S., Wilkins, J., Weiler, T., Sangster, K. et al., Urine protein profiling with surface-enhanced laser-desorption/ionization time-of-flight mass spectrometry. Kidney Int. 2004, 65, 323–332.
  • 21
    Mischak, H., Julian, B. A., Novak, J., High-resolution proteome/peptidome analysis of peptides and low-molecular-weight proteins in urine. Proteomics Clin. Appl. 2007, 1, 792–804.
    Direct Link:
  • 22
    Thongboonkerd, V., Recent progress in urinary proteomics. Proteomics Clin. Appl. 2007, 1, 780–791.
    Direct Link:
  • 23
    Chalmers, M. J., Kolch, W., Emmett, M. R., Marshall, A. G., Mischak, H., Identification and analysis of phosphopeptides. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2004, 803, 111–120.
  • 24
    Decramer, S., Wittke, S., Mischak, H., Zurbig, P. et al., Predicting the clinical outcome of congenital unilateral ureteropelvic junction obstruction in newborn by urinary proteome analysis. Nat. Med. 2006, 12, 398–400.
  • 25
    Weissinger, E. M., Schiffer, E., Hertenstein, B., Ferrara, J. L. et al., Proteomic patterns predict acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Blood 2007, 109, 5511–5519.
  • 26
    Wittke, S., Haubitz, M., Walden, M., Rohde, F. et al., Detection of acute tubulointerstitial rejection by proteomic analysis of urinary samples in renal transplant recipients. Am. J. Transplant. 2005, 5, 2479–2488.
    Direct Link:
  • 27
    Mischak, H., Apweiler, R., Banks, R. E., Conaway, M. et al., Clinical proteomics: A need to define the field and to begin to set adequate standards. Proteomics Clin. Appl. 2007, 1, 148–156.
    Direct Link:
  • 28
    Taylor, C. F., Paton, N. W., Lilley, K. S., Binz, P. A. et al., The minimum information about a proteomics experiment (MIAPE). Nat. Biotechnol. 2007, 25, 887–893.
  • 29
    Girasole, C. R., Cookson, M. S., Putzi, M. J., Chang, S. S. et al., Significance of atypical and suspicious small acinar proliferations, and high grade prostatic intraepithelial neoplasia on prostate biopsy: Implications for cancer detection and biopsy strategy. J. Urol. 2006, 175, 929–933.
  • 30
    Epstein, J. I., Herawi, M., Prostate needle biopsies containing prostatic intraepithelial neoplasia or atypical foci suspicious for carcinoma: Implications for patient care. J. Urol. 2006, 175, 820–834.
  • 31
    Obiezu, C. V., Shan, S. J., Soosaipillai, A., Luo, L. Y. et al., Human kallikrein 4: Quantitative study in tissues and evidence for its secretion into biological fluids. Clin. Chem. 2005, 51, 1432–1442.
  • 32
    Acevedo, B., Perera, Y., Torres, E., Penton, D. et al., Fast and novel purification method to obtain the prostate specific antigen (PSA) from human seminal plasma. Prostate 2006, 66, 1029–1036.
    Direct Link:
  • 33
    Weissinger, E. M., Wittke, S., Kaiser, T., Haller, H. et al., Proteomic patterns established with capillary electrophoresis and mass spectrometry for diagnostic purposes. Kidney Int. 2004, 65, 2426–2434.
  • 34
    Theodorescu, D., Fliser, D., Wittke, S., Mischak, H. et al., Pilot study of capillary electrophoresis coupled to mass spectrometry as a tool to define potential prostate cancer biomarkers in urine. Electrophoresis 2005, 26, 2797–2808.
    Direct Link:
  • 35
    DeLeo, J. M., Receiver operating characteristic laboratory (ROCLAB): Software for developing decision strategies that account for uncertainty. Second International Symposium on Uncertainty Modeling and Analysis, College Park, MD, USA, April 25, 1993, pp. 318–325.
  • 36
    Benjamini, Y., Hochberg, Y., Controlling the false discovery rate: A practical and powerful approach to multiple testing. J. R. Stat. Soc. B (Methodological) 1995, 57, 125–133.
  • 37
    Mukherjee, S., Kashino, S. S., Zhang, Y., Daifalla, N. et al., Cloning of the gene encoding a protective Mycobacterium tuberculosis secreted protein detected in vivo during the initial phases of the infectious process. J. Immunol. 2005, 175, 5298–5305.
  • 38
    Weissinger, E. M., Kaiser, T., Meert, N., De Smet, R. et al., Proteomics: A novel tool to unravel the patho-physiology of uraemia. Nephrol. Dial. Transplant. 2004, 19, 3068–3077.
  • 39
    Dieterle, F., Muller-Hagedorn, S., Liebich, H. M., Gauglitz, G., Urinary nucleosides as potential tumor markers evaluated by learning vector quantization. Artif. Intell. Med. 2003, 28, 265–279.
  • 40
    Brown, M. P., Grundy, W. N., Lin, D., Cristianini, N. et al., Knowledge-based analysis of microarray gene expression data by using support vector machines. Proc. Natl. Acad. Sci. USA 2000, 97, 262–267.
  • 41
    Zürbig, P., Renfrow, M. B., Schiffer, E., Novak, J. et al., Biomarker discovery by CE-MS enables sequence analysis via MS/MS with platform-independent separation. Electrophoresis 2006, 27, 2111–2125.
    Direct Link:
  • 42
    Coon, J. J., Shabanowitz, J., Hunt, D. F., Syka, J. E., Electron transfer dissociation of peptide anions. J. Am. Soc. Mass Spectrom. 2005, 16, 880–882.
  • 43
    Syka, J. E., Coon, J. J., Schroeder, M. J., Shabanowitz, J., Hunt, D. F., Peptide and protein sequence analysis by electron transfer dissociation mass spectrometry. Proc. Natl. Acad. Sci. USA 2004, 101, 9528–9533.
  • 44
    Lilja, H., Structure and function of prostatic- and seminal vesicle-secreted proteins involved in the gelation and liquefaction of human semen. Scand. J. Clin. Lab. Invest. Suppl. 1988, 191, 13–20.
  • 45
    Lilja, H., Cell biology of semenogelin. Andrologia 1990, 22, 132–141.
    Direct Link:
  • 46
    Lodding, P., Aus, G., Bergdahl, S., Frosing, R. et al., Characteristics of screening detected prostate cancer in men 50 to 66 years old with 3 to 4 ng/ml. Prostate specific antigen. J. Urol. 1998, 159, 899–903.
  • 47
    Punglia, R. S., D'Amico, A. V., Catalona, W. J., Roehl, K. A., Kuntz, K. M., Effect of verification bias on screening for prostate cancer by measurement of prostate-specific antigen. N. Engl. J. Med. 2003, 349, 335–342.
  • 48
    Roehl, K. A., Antenor, J. A., Catalona, W. J., Serial biopsy results in prostate cancer screening study. J. Urol. 2002, 167, 2435–2439.
  • 49
    Amsellem-Ouazana, D., Younes, P., Conquy, S., Peyromaure, M. et al., Negative prostatic biopsies in patients with a high risk of prostate cancer. Is the combination of endorectal MRI and magnetic resonance spectroscopy imaging (MRSI) a useful tool? A preliminary study. Eur. Urol. 2005, 47, 582–586.
  • 50
    Anastasiadis, A. G., Lichy, M. P., Nagele, U., Kuczyk, M. A. et al., MRI-guided biopsy of the prostate increases diagnostic performance in men with elevated or increasing PSA levels after previous negative TRUS biopsies. Eur. Urol. 2006, 50, 738–748.
  • 51
    Chun, F. K., Karakiewicz, P. I., Briganti, A., Walz, J. et al., A critical appraisal of logistic regression-based nomograms, artificial neural networks, classification and regression-tree models, look-up tables and risk-group stratification models for prostate cancer. BJU Int. 2007, 99, 794–800.
    Direct Link:
  • 52
    Eastham, J. A., May, R., Robertson, J. L., Sartor, O., Kattan, M. W., Development of a nomogram that predicts the probability of a positive prostate biopsy in men with an abnormal digital rectal examination and a prostate-specific antigen between 0 and 4 ng/mL. Urology 1999, 54, 709–713.
  • 53
    Veltri, R. W., Miller, M. C., O'dowd, G. J., Partin, A. W., Impact of age on total and complexed prostate-specific antigen cutoffs in a contemporary referral series of men with prostate cancer. Urology 2002, 60, 47–52.
  • 54
    Lehrer, S., Roboz, J., Ding, H., Zhao, S. et al., Putative protein markers in the sera of men with prostatic neoplasms. BJU Int. 2003, 92, 223–225.
    Direct Link:
  • 55
    Liu, A. Y., Zhang, H., Sorensen, C. M., Diamond, D. L., Analysis of prostate cancer by proteomics using tissue specimens. J. Urol. 2005, 173, 73–78.
  • 56
    Semmes, O. J., Feng, Z., Adam, B. L., Banez, L. L. et al., Evaluation of serum protein profiling by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry for the detection of prostate cancer: I. Assessment of platform reproducibility. Clin. Chem. 2005, 51, 102–112.
  • 57
    Malik, G., Ward, M. D., Gupta, S. K., Trosset, M. W. et al., Serum levels of an isoform of apolipoprotein A-II as a potential marker for prostate cancer. Clin. Cancer Res. 2005, 11, 1073–1085.
  • 58
    Paul, B., Dhir, R., Landsittel, D., Hitchens, M. R., Getzenberg, R. H., Detection of prostate cancer with a blood-based assay for early prostate cancer antigen. Cancer Res. 2005, 65, 4097–4100.
  • 59
    Uetsuki, H., Tsunemori, H., Taoka, R., Haba, R. et al., Expression of a novel biomarker, EPCA, in adenocarcinomas and precancerous lesions in the prostate. J. Urol. 2005, 174, 514–518.
  • 60
    Dhir, R., Vietmeier, B., Arlotti, J., Acquafondata, M. et al., Early identification of individuals with prostate cancer in negative biopsies. J. Urol. 2004, 171, 1419–1423.
  • 61
    Fernandez, C., Rifai, N., Wenger, A. S., Mickey, D. D., Silverman, L. M., A preliminary study of urinary transferrin as a marker for prostatic cancer. Clin. Chim. Acta 1986, 161, 335–339.
  • 62
    Teni, T. R., Sheth, A. R., Kamath, M. R., Sheth, N. A., Serum and urinary prostatic inhibin-like peptide in benign prostatic hyperplasia and carcinoma of prostate. Cancer Lett. 1988, 43, 9–14.
  • 63
    Hutchinson, L. M., Chang, E. L., Becker, C. M., Ushiyama, N. et al., Development of a sensitive and specific enzyme-linked immunosorbent assay for thymosin beta15, a urinary biomarker of human prostate cancer. Clin. Biochem. 2005, 38, 558–571.
  • 64
    Rogers, C. G., Yan, G., Zha, S., Gonzalgo, M. L. et al., Prostate cancer detection on urinalysis for alpha methylacyl coenzyme a racemase protein. J. Urol. 2004, 172, 1501–1503.
  • 65
    Lwaleed, B. A., Francis, J. L., Chisholm, M., Urinary tissue factor levels in patients with bladder and prostate cancer. Eur. J. Surg. Oncol. 2000, 26, 44–49.
  • 66
    Stoeber, K., Swinn, R., Prevost, A. T., Clive-Lowe, P. et al., Diagnosis of genito-urinary tract cancer by detection of minichromosome maintenance 5 protein in urine sediments. J. Natl. Cancer Inst. 2002, 94, 1071–1079.
  • 67
    Rehman, I., Azzouzi, A. R., Catto, J. W., Allen, S. et al., Proteomic analysis of voided urine after prostatic massage from patients with prostate cancer: A pilot study. Urology 2004, 64, 1238–1243.
  • 68
    M'koma, A. E., Blum, D. L., Norris, J. L., Koyama, T. et al., Detection of preneoplastic and neoplastic prostate disease by MADI profiling of urine. Biochem. Biophys. Res. Commun. 2006, 353, 829–834.
  • 69
    Blok, L. J., Chang, G. T., Steenbeek-Slotboom, M., van Weerden, W. M. et al., Regulation of expression of Na+,K+-ATPase in androgen-dependent and androgen-independent prostate cancer. Br. J. Cancer 1999, 81, 28–36.
  • 70
    Sternlicht, M. D., Werb, Z., How matrix metalloproteinases regulate cell behavior. Annu. Rev. Cell Dev. Biol. 2001, 17, 463–516.
  • 71
    Brew, K., Dinakarpandian, D., Nagase, H., Tissue inhibitors of metalloproteinases: Evolution, structure and function. Biochim. Biophys. Acta 2000, 1477, 267–283.
  • 72
    Hu, R., Wu, R., Deng, J., Lau, D., A small proline-rich protein, spr1: Specific marker for squamous lung carcinoma. Lung Cancer 1998, 20, 25–30.
  • 73
    Lau, D., Guo, L., Chan, A., Wu, R., SPR1. An early molecular marker for bronchial carcinogenesis. Methods Mol. Med. 2003, 75, 397–403.
  • 74
    Lau, D., Xue, L., Hu, R., Liaw, T. et al., Expression and regulation of a molecular marker, SPR1, in multistep bronchial carcinogenesis. Am. J. Respir. Cell Mol. Biol. 2000, 22, 92–96.
  • 75
    DeMuth, J. P., Weaver, D. A., Crawford, E. L., Jackson, C. M., Willey, J. C., Loss of spr1 expression measurable by quantitative RT-PCR in human bronchogenic carcinoma cell lines. Am. J. Respir. Cell Mol. Biol. 1998, 19, 25–29.
Get PDF (528K)