Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

New circulating biomarkers for prostate cancer

Prostate Cancer and Prostatic Diseases volume 11, pages 112–120 (2008)Cite this article

Abstract

The introduction of prostate-specific antigen (PSA) revolutionized prostate cancer (PCa) screening and ushered the PSA era. However, its use as a screening tool remains controversial and changes in the epidemiology of PCa have strongly limited its prognostic role. Therefore, we need novel approaches to improve our ability to detect PCa and foretell the course of the disease. To improve the specificity of total PSA, several approaches based on PSA derivatives have been investigated such as age-specific values, PSA density (PSAD), PSAD of the transition zone, PSA velocity and assessment of various isoforms of PSA. With recent advances in biotechnology such as high-throughput molecular analyses, many potential blood biomarkers have been identified and are currently under investigation. Given the plethora of candidate PCa biomarkers, we have chosen to discuss a select group of candidate blood-based biomarkers including human glandular kallikrein, early prostate cancer antigens, insulin-like growth factor-I (IGF-I) and its binding proteins (IGFBP-2 and IGFBP-3), urokinase plasminogen activation system, transforming growth factor-β1, interleukin-6, chromogranin A, prostate secretory protein, prostate-specific membrane antigen, PCa-specific autoantibodies and α-methylacyl-CoA racemase. While these and other markers have shown promise in early phase studies, no single biomarker is likely to have the appropriate degree of certainty to dictate treatment decisions. Consequently, the future of cancer prognosis may rely on small panels of markers that can accurately predict PCa presence, stage, metastasis, and serve as prognosticators, targets and/or surrogate end points of disease progression and response to therapy.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ . Cancer statistics, 2007. CA Cancer J Clin 2007; 57: 43–66.

    Article  PubMed  Google Scholar 

  2. Ross KS, Carter HB, Pearson JD, Guess HA . Comparative efficiency of prostate-specific antigen screening strategies for prostate cancer detection. JAMA 2000; 284: 1399–1405.

    CAS  PubMed  Google Scholar 

  3. Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG et al. The influence of finasteride on the development of prostate cancer. N Engl J Med 2003; 349: 215–224.

    CAS  PubMed  Google Scholar 

  4. Stamey TA, Caldwell M, McNeal JE, Nolley R, Hemenez M, Downs J . The prostate specific antigen era in the United States is over for prostate cancer: what happened in the last 20 years? J Urol 2004; 172 (4 Part 1): 1297–1301.

    PubMed  Google Scholar 

  5. Roehrborn CG, McConnell JD, Lieber M, Kaplan S, Geller J, Malek GH et al. Serum prostate-specific antigen concentration is a powerful predictor of acute urinary retention and need for surgery in men with clinical benign prostatic hyperplasia. PLESS Study Group. Urology 1999; 53: 473–480.

    CAS  PubMed  Google Scholar 

  6. Roehrborn CG, McConnell J, Bonilla J, Rosenblatt S, Hudson PB, Malek GH et al. Serum prostate specific antigen is a strong predictor of future prostate growth in men with benign prostatic hyperplasia. PROSCAR long-term efficacy and safety study. J Urol 2000; 163: 13–20.

    CAS  PubMed  Google Scholar 

  7. Roehrborn CG, Boyle P, Gould AL, Waldstreicher J . Serum prostate-specific antigen as a predictor of prostate volume in men with benign prostatic hyperplasia. Urology 1999; 53: 581–589.

    CAS  PubMed  Google Scholar 

  8. Noguchi M, Stamey TA, McNeal JE, Yemoto CM . Preoperative serum prostate specific antigen does not reflect biochemical failure rates after radical prostatectomy in men with large volume cancers. J Urol 2000; 164: 1596–1600.

    CAS  PubMed  Google Scholar 

  9. Shariat SF, Abdel-Aziz KF, Roehrborn CG, Lotan Y . Pre-operative percent free PSA predicts clinical outcomes in patients treated with radical prostatectomy with total PSA levels below 10 ng/ml. Eur Urol 2006; 49: 293–302.

    PubMed  Google Scholar 

  10. Stamey TA, Johnstone IM, McNeal JE, Lu AY, Yemoto CM . Preoperative serum prostate specific antigen levels between 2 and 22 ng/ml correlate poorly with post-radical prostatectomy cancer morphology: prostate specific antigen cure rates appear constant between 2 and 9 ng/ml. J Urol 2002; 167: 103–111.

    CAS  PubMed  Google Scholar 

  11. Aihara M, Lebovitz RM, Wheeler TM, Kinner BM, Ohori M, Scardino PT . Prostate specific antigen and Gleason grade: an immunohistochemical study of prostate cancer. J Urol 1994; 151: 1558–1564.

    CAS  PubMed  Google Scholar 

  12. Darson MF, Pacelli A, Roche P, Rittenhouse HG, Wolfert RL, Young CY et al. Human glandular kallikrein 2 (hK2) expression in prostatic intraepithelial neoplasia and adenocarcinoma: a novel prostate cancer marker. Urology 1997; 49: 857–862.

    CAS  PubMed  Google Scholar 

  13. Partin AW, Mangold LA, Lamm DM, Walsh PC, Epstein JI, Pearson JD . Contemporary update of prostate cancer staging nomograms (Partin Tables) for the new millennium. Urology 2001; 58: 843–848.

    CAS  PubMed  Google Scholar 

  14. Kattan MW, Eastham JA, Stapleton AM, Wheeler TM, Scardino PT . A preoperative nomogram for disease recurrence following radical prostatectomy for prostate cancer. J Natl Cancer Inst 1998; 90: 766–771.

    CAS  PubMed  Google Scholar 

  15. Kattan MW, Wheeler TM, Scardino PT . Postoperative nomogram for disease recurrence after radical prostatectomy for prostate cancer. J Clin Oncol 1999; 17: 1499–1507.

    CAS  PubMed  Google Scholar 

  16. Kattan MW, Zelefsky MJ, Kupelian PA, Scardino PT, Fuks Z, Leibel SA . Pretreatment nomogram for predicting the outcome of three-dimensional conformal radiotherapy in prostate cancer. J Clin Oncol 2000; 18: 3352–3359.

    CAS  PubMed  Google Scholar 

  17. Hernandez J, Thompson IM . Prostate-specific antigen: a review of the validation of the most commonly used cancer biomarker. Cancer 2004; 101: 894–904.

    CAS  PubMed  Google Scholar 

  18. Catalona WJ, Smith DS, Ratliff TL, Dodds KM, Coplen DE, Yuan JJ et al. Measurement of prostate-specific antigen in serum as a screening test for prostate cancer. N Engl J Med 1991; 324: 1156–1161.

    CAS  PubMed  Google Scholar 

  19. Canto EI, Singh H, Shariat SF, Kadmon D, Miles BJ, Wheeler TM et al. Effects of systematic 12-core biopsy on the performance of percent free prostate specific antigen for prostate cancer detection. J Urol 2004; 172: 900–904.

    PubMed  Google Scholar 

  20. Thompson IM, Ankerst DP, Chi C, Lucia MS, Goodman PJ, Crowley JJ et al. Operating characteristics of prostate-specific antigen in men with an initial PSA level of 3.0 ng/ml or lower. JAMA 2005; 294: 66–70.

    CAS  PubMed  Google Scholar 

  21. Oesterling JE, Jacobsen SJ, Chute CG, Guess HA, Girman CJ, Panser LA et al. Serum prostate-specific antigen in a community-based population of healthy men. Establishment of age-specific reference ranges. JAMA 1993; 270: 860–864.

    CAS  PubMed  Google Scholar 

  22. Bassler Jr TJ, Orozco R, Bassler IC, O'Dowd GJ, Stamey TA . Most prostate cancers missed by raising the upper limit of normal prostate-specific antigen for men in their sixties are clinically significant. Urology 1998; 52: 1064–1069.

    PubMed  Google Scholar 

  23. Etzioni R, Shen Y, Petteway JC, Brawer MK . Age-specific prostate-specific antigen: a reassessment. Prostate (Suppl) 1996; 7: 70–77.

    CAS  Google Scholar 

  24. Bangma CH, Kranse R, Blijenberg BG, Schroder FH . The value of screening tests in the detection of prostate cancer. Part I: results of a retrospective evaluation of 1726 men. Urology 1995; 46: 773–778.

    CAS  PubMed  Google Scholar 

  25. Benson MC, Whang IS, Pantuck A, Ring K, Kaplan SA, Olsson CA et al. Prostate specific antigen density: a means of distinguishing benign prostatic hypertrophy and prostate cancer. J Urol 1992; 147 (3 Part 2): 815–816.

    CAS  PubMed  Google Scholar 

  26. Catalona WJ, Richie JP, deKernion JB, Ahmann FR, Ratliff TL, Dalkin BL et al. Comparison of prostate specific antigen concentration versus prostate specific antigen density in the early detection of prostate cancer: receiver operating characteristic curves. J Urol 1994; 152 (6 Part 1): 2031–2036.

    CAS  PubMed  Google Scholar 

  27. Mettlin C, Littrup PJ, Kane RA, Murphy GP, Lee F, Chesley A et al. Relative sensitivity and specificity of serum prostate specific antigen (PSA) level compared with age-referenced PSA, PSA density, and PSA change. Data from the American Cancer Society National Prostate Cancer Detection Project. Cancer 1994; 74: 1615–1620.

    CAS  PubMed  Google Scholar 

  28. Djavan B, Zlotta AR, Byttebier G, Shariat S, Omar M, Schulman CC et al. Prostate specific antigen density of the transition zone for early detection of prostate cancer. J Urol 1998; 160: 411–418;discussion 418–9.

    CAS  PubMed  Google Scholar 

  29. Carter HB, Pearson JD, Metter EJ, Brant LJ, Chan DW, Andres R et al. Longitudinal evaluation of prostate-specific antigen levels in men with and without prostate disease. JAMA 1992; 267: 2215–2220.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Roehrborn CG, Pickens GJ, Carmody III T . Variability of repeated serum prostate-specific antigen (PSA) measurements within less than 90 days in a well-defined patient population. Urology 1996; 47: 59–66.

    CAS  PubMed  Google Scholar 

  31. Link RE, Shariat SF, Nguyen CV, Farr A, Weinberg AD, Morton RA et al. Variation in prostate specific antigen results from 2 different assay platforms: clinical impact on 2304 patients undergoing prostate cancer screening. J Urol 2004; 171 (6 Part 1): 2234–2238.

    CAS  PubMed  Google Scholar 

  32. Carter HB, Pearson JD, Waclawiw Z, Metter EJ, Chan DW, Guess HA et al. Prostate-specific antigen variability in men without prostate cancer: effect of sampling interval on prostate-specific antigen velocity. Urology 1995; 45: 591–596.

    CAS  PubMed  Google Scholar 

  33. D'Amico AV, Chen MH, Roehl KA, Catalona WJ . Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy. N Engl J Med 2004; 351: 125–135.

    CAS  PubMed  Google Scholar 

  34. D'Amico AV, Renshaw AA, Sussman B, Chen MH . Pretreatment PSA velocity and risk of death from prostate cancer following external beam radiation therapy. JAMA 2005; 294: 440–447.

    CAS  PubMed  Google Scholar 

  35. Patel DA, Presti Jr JC, McNeal JE, Gill H, Brooks JD, King CR . Preoperative PSA velocity is an independent prognostic factor for relapse after radical prostatectomy. J Clin Oncol 2005; 23: 6157–6162.

    PubMed  Google Scholar 

  36. Allard WJ, Zhou Z, Yeung KK . Novel immunoassay for the measurement of complexed prostate-specific antigen in serum. Clin Chem 1998; 44 (6 Part 1): 1216–1223.

    CAS  PubMed  Google Scholar 

  37. Horninger W, Cheli CD, Babaian RJ, Fritsche HA, Lepor H, Taneja SS et al. Complexed prostate-specific antigen for early detection of prostate cancer in men with serum prostate-specific antigen levels of 2–4 nanograms per milliliter. Urology 2002; 60 (4 Suppl 1): 31–35.

    PubMed  Google Scholar 

  38. Lein M, Kwiatkowski M, Semjonow A, Luboldt HJ, Hammerer P, Stephan C et al. A multicenter clinical trial on the use of complexed prostate specific antigen in low prostate specific antigen concentrations. J Urol 2003; 170 (4 Part 1): 1175–1179.

    CAS  PubMed  Google Scholar 

  39. Brawer MK, Meyer GE, Letran JL, Bankson DD, Morris DL, Yeung KK et al. Measurement of complexed PSA improves specificity for early detection of prostate cancer. Urology 1998; 52: 372–378.

    CAS  PubMed  Google Scholar 

  40. Partin AW, Brawer MK, Bartsch G, Horninger W, Taneja SS, Lepor H et al. Complexed prostate specific antigen improves specificity for prostate cancer detection: results of a prospective multicenter clinical trial. J Urol 2003; 170: 1787–1791.

    PubMed  Google Scholar 

  41. Catalona WJ, Partin AW, Slawin KM, Brawer MK, Flanigan RC, Patel A et al. Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter clinical trial. JAMA 1998; 279: 1542–1547.

    CAS  PubMed  Google Scholar 

  42. Catalona WJ, Southwick PC, Slawin KM, Partin AW, Brawer MK, Flanigan RC et al. Comparison of percent free PSA, PSA density, and age-specific PSA cutoffs for prostate cancer detection and staging. Urology 2000; 56: 255–260.

    CAS  PubMed  Google Scholar 

  43. Graefen M, Karakiewicz PI, Cagiannos I, Hammerer PG, Haese A, Palisaar J et al. Percent free prostate specific antigen is not an independent predictor of organ confinement or prostate specific antigen recurrence in unscreened patients with localized prostate cancer treated with radical prostatectomy. J Urol 2002; 167: 1306–1309.

    PubMed  Google Scholar 

  44. Mikolajczyk SD, Marks LS, Partin AW, Rittenhouse HG . Free prostate-specific antigen in serum is becoming more complex. Urology 2002; 59: 797–802.

    PubMed  Google Scholar 

  45. Mikolajczyk SD, Millar LS, Wang TJ, Rittenhouse HG, Wolfert RL, Marks LS et al. ‘BPSA,’ a specific molecular form of free prostate-specific antigen, is found predominantly in the transition zone of patients with nodular benign prostatic hyperplasia. Urology 2000; 55: 41–45.

    CAS  PubMed  Google Scholar 

  46. Canto EI, Singh H, Shariat SF, Lamb DJ, Mikolajczyk SD, Linton HJ et al. Serum BPSA outperforms both total PSA and free PSA as a predictor of prostatic enlargement in men without prostate cancer. Urology 2004; 63: 905–910; discussion 910–911.

    PubMed  Google Scholar 

  47. Catalona WJ, Bartsch G, Rittenhouse HG, Evans CL, Linton HJ, Amirkhan A et al. Serum pro prostate specific antigen improves cancer detection compared to free and complexed prostate specific antigen in men with prostate specific antigen 2–4 ng/ml. J Urol 2003; 170 (6 Part 1): 2181–2185.

    CAS  PubMed  Google Scholar 

  48. Sokoll LJ, Chan DW, Mikolajczyk SD, Rittenhouse HG, Evans CL, Linton HJ et al. Proenzyme psa for the early detection of prostate cancer in the 2.5–4.0 ng/ml total psa range: preliminary analysis. Urology 2003; 61: 274–276.

    PubMed  Google Scholar 

  49. Catalona WJ, Bartsch G, Rittenhouse HG, Evans CL, Linton HJ, Horninger W et al. Serum pro-prostate specific antigen preferentially detects aggressive prostate cancers in men with 2–4 ng/ml prostate specific antigen. J Urol 2004; 171 (6 Part 1): 2239–2244.

    PubMed  Google Scholar 

  50. Nurmikko P, Pettersson K, Piironen T, Hugosson J, Lilja H . Discrimination of prostate cancer from benign disease by plasma measurement of intact, free prostate-specific antigen lacking an internal cleavage site at Lys145-Lys146. Clin Chem 2001; 47: 1415–1423.

    CAS  PubMed  Google Scholar 

  51. Yousef GM, Diamandis EP . The new human tissue kallikrein gene family: structure, function, and association to disease. Endocr Rev 2001; 22: 184–204.

    CAS  PubMed  Google Scholar 

  52. Nam RK, Diamandis EP, Toi A, Trachtenberg J, Magklara A, Scorilas A et al. Serum human glandular kallikrein-2 protease levels predict the presence of prostate cancer among men with elevated prostate-specific antigen. J Clin Oncol 2000; 18: 1036–1042.

    CAS  PubMed  Google Scholar 

  53. Becker C, Piironen T, Pettersson K, Hugosson J, Lilja H . Clinical value of human glandular kallikrein 2 and free and total prostate-specific antigen in serum from a population of men with prostate-specific antigen levels 3.0 ng/ml or greater. Urology 2000; 55: 694–699.

    CAS  PubMed  Google Scholar 

  54. Becker C, Piironen T, Pettersson K, Bjork T, Wojno KJ, Oesterling JE et al. Discrimination of men with prostate cancer from those with benign disease by measurements of human glandular kallikrein 2 (HK2) in serum. J Urol 2000; 163: 311–316.

    CAS  PubMed  Google Scholar 

  55. Haese A, Graefen M, Steuber T, Becker C, Pettersson K, Piironen T et al. Human glandular kallikrein 2 levels in serum for discrimination of pathologically organ-confined from locally-advanced prostate cancer in total PSA-levels below 10 ng/ml. Prostate 2001; 49: 101–109.

    CAS  PubMed  Google Scholar 

  56. Kwiatkowski MK, Recker F, Piironen T, Pettersson K, Otto T, Wernli M et al. In prostatism patients the ratio of human glandular kallikrein to free PSA improves the discrimination between prostate cancer and benign hyperplasia within the diagnostic ‘gray zone’ of total PSA 4–10 ng/ml. Urology 1998; 52: 360–365.

    CAS  PubMed  Google Scholar 

  57. Recker F, Kwiatkowski MK, Piironen T, Pettersson K, Lummen G, Wernli M et al. The importance of human glandular kallikrein and its correlation with different prostate specific antigen serum forms in the detection of prostate carcinoma. Cancer 1998; 83: 2540–2547.

    CAS  PubMed  Google Scholar 

  58. Kurek R, Nunez G, Tselis N, Konrad L, Martin T, Roeddiger S et al. Prognostic value of combined ‘triple’-reverse transcription-PCR analysis for prostate-specific antigen, human kallikrein 2, and prostate-specific membrane antigen mRNA in peripheral blood and lymph nodes of prostate cancer patients. Clin Cancer Res 2004; 10: 5808–5814.

    CAS  PubMed  Google Scholar 

  59. Getzenberg RH, Pienta KJ, Huang EY, Coffey DS . Identification of nuclear matrix proteins in the cancer and normal rat prostate. Cancer Res 1991; 51: 6514–6520.

    CAS  PubMed  Google Scholar 

  60. Dhir R, Vietmeier B, Arlotti J, Acquafondata M, Landsittel D, Masterson R et al. Early identification of individuals with prostate cancer in negative biopsies. J Urol 2004; 171: 1419–1423.

    PubMed  Google Scholar 

  61. Uetsuki H, Tsunemori H, Taoka R, Haba R, Ishikawa M, Kakehi Y . Expression of a novel biomarker, EPCA, in adenocarcinomas and precancerous lesions in the prostate. J Urol 2005; 174: 514–518.

    PubMed  Google Scholar 

  62. Paul B, Dhir R, Landsittel D, Hitchens MR, Getzenberg RH . Detection of prostate cancer with a blood-based assay for early prostate cancer antigen. Cancer Res 2005; 65: 4097–4100.

    CAS  PubMed  Google Scholar 

  63. Leman ES, Cannon GW, Trock BJ, Sokoll LJ, Chan DW, Mangold L et al. EPCA-2: a highly specific serum marker for prostate cancer. Urology 2007; 69: 714–720.

    PubMed  Google Scholar 

  64. Duffy MJ . Urokinase-type plasminogen activator: a potent marker of metastatic potential in human cancers. Biochem Soc Trans 2002; 30: 207–210.

    CAS  PubMed  Google Scholar 

  65. Stephens RW, Nielsen HJ, Christensen IJ, Thorlacius-Ussing O, Sorensen S, Dano K et al. Plasma urokinase receptor levels in patients with colorectal cancer: relationship to prognosis. J Natl Cancer Inst 1999; 91: 869–874.

    CAS  PubMed  Google Scholar 

  66. McCabe NP, Angwafo III FF, Zaher A, Selman SH, Kouinche A, Jankun J . Expression of soluble urokinase plasminogen activator receptor may be related to outcome in prostate cancer patients. Oncol Rep 2000; 7: 879–882.

    CAS  PubMed  Google Scholar 

  67. Steuber T, Vickers A, Haese A, Kattan MW, Eastham JA, Scardino PT et al. Free PSA isoforms and intact and cleaved forms of urokinase plasminogen activator receptor in serum improve selection of patients for prostate cancer biopsy. Int J Cancer 2007; 120: 1499–1504.

    CAS  PubMed  Google Scholar 

  68. Hienert G, Kirchheimer JC, Pfluger H, Binder BR . Urokinase-type plasminogen activator as a marker for the formation of distant metastases in prostatic carcinomas. J Urol 1988; 140: 1466–1469.

    CAS  PubMed  Google Scholar 

  69. Miyake H, Hara I, Yamanaka K, Gohji K, Arakawa S, Kamidono S . Elevation of serum levels of urokinase-type plasminogen activator and its receptor is associated with disease progression and prognosis in patients with prostate cancer. Prostate 1999; 39: 123–129.

    CAS  PubMed  Google Scholar 

  70. Shariat SF, Roehrborn CG, McConnell JD, Park S, Alam N, Wheeler TM et al. Association of the circulating levels of the urokinase system of plasminogen activation with the presence of prostate cancer and invasion, progression, and metastasis. J Clin Oncol 2007; 25: 349–355.

    CAS  PubMed  Google Scholar 

  71. Shariat SF, Shalev M, Menesses-Diaz A, Kim IY, Kattan MW, Wheeler TM et al. Preoperative plasma levels of transforming growth factor beta(1) (TGF-beta(1)) strongly predict progression in patients undergoing radical prostatectomy. J Clin Oncol 2001; 19: 2856–2864.

    CAS  PubMed  Google Scholar 

  72. Morton DM, Barrack ER . Modulation of transforming growth factor beta 1 effects on prostate cancer cell proliferation by growth factors and extracellular matrix. Cancer Res 1995; 55: 2596–2602.

    CAS  PubMed  Google Scholar 

  73. Truong LD, Kadmon D, McCune BK, Flanders KC, Scardino PT, Thompson TC . Association of transforming growth factor-beta 1 with prostate cancer: an immunohistochemical study. Hum Pathol 1993; 24: 4–9.

    CAS  PubMed  Google Scholar 

  74. Shariat SF, Kattan MW, Traxel E, Andrews B, Zhu K, Wheeler TM et al. Association of pre- and postoperative plasma levels of transforming growth factor beta(1) and interleukin 6 and its soluble receptor with prostate cancer progression. Clin Cancer Res 2004; 10: 1992–1999.

    CAS  PubMed  Google Scholar 

  75. Shariat SF, Kim JH, Andrews B, Kattan MW, Wheeler TM, Kim IY et al. Preoperative plasma levels of transforming growth factor beta(1) strongly predict clinical outcome in patients with bladder carcinoma. Cancer 2001; 92: 2985–2992.

    CAS  PubMed  Google Scholar 

  76. Ivanovic V, Melman A, Davis-Joseph B, Valcic M, Geliebter J . Elevated plasma levels of TGF-beta 1 in patients with invasive prostate cancer. Nat Med 1995; 1: 282–284.

    CAS  PubMed  Google Scholar 

  77. Wolff JM, Fandel TH, Borchers H, Jakse G . Serum concentrations of transforming growth factor-beta 1 in patients with benign and malignant prostatic diseases. Anticancer Res 1999; 19: 2657–2659.

    CAS  PubMed  Google Scholar 

  78. Perry KT, Anthony CT, Case T, Steiner MS . Transforming growth factor beta as a clinical biomarker for prostate cancer. Urology 1997; 49: 151–155.

    CAS  PubMed  Google Scholar 

  79. Akira S, Taga T, Kishimoto T . Interleukin-6 in biology and medicine. Adv Immunol 1993; 54: 1–78.

    CAS  PubMed  Google Scholar 

  80. Hobisch A, Eder IE, Putz T, Horninger W, Bartsch G, Klocker H et al. Interleukin-6 regulates prostate-specific protein expression in prostate carcinoma cells by activation of the androgen receptor. Cancer Res 1998; 58: 4640–4645.

    CAS  PubMed  Google Scholar 

  81. Giri D, Ozen M, Ittmann M . Interleukin-6 is an autocrine growth factor in human prostate cancer. Am J Pathol 2001; 159: 2159–2165.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Michalaki V, Syrigos K, Charles P, Waxman J . Serum levels of IL-6 and TNF-alpha correlate with clinicopathological features and patient survival in patients with prostate cancer. Br J Cancer 2004; 90: 2312–2316.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Nakashima J, Tachibana M, Horiguchi Y, Oya M, Ohigashi T, Asakura H et al. Serum interleukin 6 as a prognostic factor in patients with prostate cancer. Clin Cancer Res 2000; 6: 2702–2706.

    CAS  PubMed  Google Scholar 

  84. Kattan MW, Shariat SF, Andrews B, Zhu K, Canto E, Matsumoto K et al. The addition of interleukin-6 soluble receptor and transforming growth factor beta1 improves a preoperative nomogram for predicting biochemical progression in patients with clinically localized prostate cancer. J Clin Oncol 2003; 21: 3573–3579.

    CAS  PubMed  Google Scholar 

  85. Fracalanza S, Prayer-Galetti T, Pinto F, Navaglia F, Sacco E, Ciaccia M et al. Plasma chromogranin A in patients with prostate cancer improves the diagnostic efficacy of free/total prostate-specific antigen determination. Urol Int 2005; 75: 57–61.

    CAS  PubMed  Google Scholar 

  86. Marszalek M, Wachter J, Ponholzer A, Leitha T, Rauchenwald M, Madersbacher S . Insulin-like growth factor 1, chromogranin A and prostate specific antigen serum levels in prostate cancer patients and controls. Eur Urol 2005; 48: 34–39.

    CAS  PubMed  Google Scholar 

  87. Berruti A, Mosca A, Tucci M, Terrone C, Torta M, Tarabuzzi R et al. Independent prognostic role of circulating chromogranin A in prostate cancer patients with hormone-refractory disease. Endocr Relat Cancer 2005; 12: 109–117.

    CAS  PubMed  Google Scholar 

  88. Isshiki S, Akakura K, Komiya A, Suzuki H, Kamiya N, Ito H . Chromogranin a concentration as a serum marker to predict prognosis after endocrine therapy for prostate cancer. J Urol 2002; 167 (2 Part 1): 512–515.

    CAS  PubMed  Google Scholar 

  89. Taplin ME, George DJ, Halabi S, Sanford B, Febbo PG, Hennessy KT et al. Prognostic significance of plasma chromogranin a levels in patients with hormone-refractory prostate cancer treated in Cancer and Leukemia Group B 9480 study. Urology 2005; 66: 386–391.

    PubMed  Google Scholar 

  90. Ferrero-Pous M, Hersant AM, Pecking A, Bresard-Leroy M, Pichon MF . Serum chromogranin-A in advanced prostate cancer. BJU Int 2001; 88: 790–796.

    CAS  PubMed  Google Scholar 

  91. Sasaki T, Komiya A, Suzuki H, Shimbo M, Ueda T, Akakura K et al. Changes in chromogranin a serum levels during endocrine therapy in metastatic prostate cancer patients. Eur Urol 2005; 48: 224–229;discussion 229–30.

    CAS  PubMed  Google Scholar 

  92. Reeves JR, Dulude H, Panchal C, Daigneault L, Ramnani DM . Prognostic value of prostate secretory protein of 94 amino acids and its binding protein after radical prostatectomy. Clin Cancer Res 2006; 12 (20 Part 1): 6018–6022.

    CAS  PubMed  Google Scholar 

  93. Horoszewicz JS, Kawinski E, Murphy GP . Monoclonal antibodies to a new antigenic marker in epithelial prostatic cells and serum of prostatic cancer patients. Anticancer Res 1987; 7: 927–935.

    CAS  PubMed  Google Scholar 

  94. Murphy GP, Barren RJ, Erickson SJ, Bowes VA, Wolfert RL, Bartsch G et al. Evaluation and comparison of two new prostate carcinoma markers. Free-prostate specific antigen and prostate specific membrane antigen. Cancer 1996; 78: 809–818.

    CAS  PubMed  Google Scholar 

  95. Murphy GP, Elgamal AA, Su SL, Bostwick DG, Holmes EH . Current evaluation of the tissue localization and diagnostic utility of prostate specific membrane antigen. Cancer 1998; 83: 2259–2269.

    CAS  PubMed  Google Scholar 

  96. Beckett ML, Cazares LH, Vlahou A, Schellhammer PF, Wright Jr GL . Prostate-specific membrane antigen levels in sera from healthy men and patients with benign prostate hyperplasia or prostate cancer. Clin Cancer Res 1999; 5: 4034–4040.

    CAS  PubMed  Google Scholar 

  97. Elgamal AA, Holmes EH, Su SL, Tino WT, Simmons SJ, Peterson M et al. Prostate-specific membrane antigen (PSMA): current benefits and future value. Semin Surg Oncol 2000; 18: 10–16.

    CAS  PubMed  Google Scholar 

  98. Rubin MA, Zhou M, Dhanasekaran SM, Varambally S, Barrette TR, Sanda MG et al. Alpha-methylacyl coenzyme A racemase as a tissue biomarker for prostate cancer. JAMA 2002; 287: 1662–1670.

    CAS  PubMed  Google Scholar 

  99. Jiang Z, Wu CL, Woda BA, Iczkowski KA, Chu PG, Tretiakova MS et al. Alpha-methylacyl-CoA racemase: a multi-institutional study of a new prostate cancer marker. Histopathology 2004; 45: 218–225.

    CAS  PubMed  Google Scholar 

  100. Sreekumar A, Laxman B, Rhodes DR, Bhagavathula S, Harwood J, Giacherio D et al. Humoral immune response to alpha-methylacyl-CoA racemase and prostate cancer. J Natl Cancer Inst 2004; 96: 834–843.

    CAS  PubMed  Google Scholar 

  101. Bradley SV, Oravecz-Wilson KI, Bougeard G, Mizukami I, Li L, Munaco AJ et al. Serum antibodies to huntingtin interacting protein-1: a new blood test for prostate cancer. Cancer Res 2005; 65: 4126–4133.

    CAS  PubMed  Google Scholar 

  102. Wang X, Yu J, Sreekumar A, Varambally S, Shen R, Giacherio D et al. Autoantibody signatures in prostate cancer. N Engl J Med 2005; 353: 1224–1235.

    CAS  PubMed  Google Scholar 

  103. Chan JM, Stampfer MJ, Giovannucci E, Gann PH, Ma J, Wilkinson P et al. Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 1998; 279: 563–566.

    CAS  PubMed  Google Scholar 

  104. Harman SM, Metter EJ, Blackman MR, Landis PK, Carter HB . Serum levels of insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-3, and prostate-specific antigen as predictors of clinical prostate cancer. J Clin Endocrinol Metab 2000; 85: 4258–4265.

    CAS  PubMed  Google Scholar 

  105. Shariat SF, Lamb DJ, Kattan MW, Nguyen C, Kim J, Beck J et al. Association of preoperative plasma levels of insulin-like growth factor I and insulin-like growth factor binding proteins-2 and -3 with prostate cancer invasion, progression, and metastasis. J Clin Oncol 2002; 20: 833–841.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    K Bensalah, Y Lotan, J A Karam & S F Shariat

Authors
  1. K Bensalah
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y Lotan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J A Karam
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S F Shariat
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S F Shariat.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bensalah, K., Lotan, Y., Karam, J. et al. New circulating biomarkers for prostate cancer. Prostate Cancer Prostatic Dis 11, 112–120 (2008). https://doi.org/10.1038/sj.pcan.4501026

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.pcan.4501026

Keywords

This article is cited by

Search

Advanced search

Quick links