There is a need to improve existing methods for early diagnosis of prostate cancer (CaP) and to identify men at risk for developing aggressive disease. In an effort to replace and/or supplement prostate-specific antigen many serum analytes have been examined, but with little supportive data for clinical use. Recently, technological advances in molecular assays have improved investigational outcomes and have led to the discovery of a number of prospective markers with high specificity. Further promise for providing more accurate CaP diagnosis and prognosis lies in proteomic array profiling and DNA methylation assays. This review illustrates the current benefits and limitations of potentially useful CaP serum markers that have considerable existing data and touches upon other future markers as well as the field of proteomics.
Your institute does not have access to this article
Subscribe to Journal
Get full journal access for 1 year
only $24.75 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ . Cancer statistics, 2007. CA Cancer J Clin 2007; 57: 43–66.
Catalona WJ . Management of cancer of the prostate. N Engl J Med 1994; 331: 996–1004.
Xue Y, Smedts F, Verhofstad A, Debruyne F, de la Rosette J, Schalken J . Cell kinetics of prostate exocrine and neuroendocrine epithelium and their differential interrelationship: new perspectives. Prostate 1998; 8: 62–73.
di Sant'Agnese PA, Cockett AT . Neuroendocrine differentiation in prostatic malignancy. Cancer 1996; 78: 357–361.
Abrahamsson PA . Neuroendocrine cells in tumour growth of the prostate. Endoc Relat Cancer 1999; 6: 503–519.
Nakada SY, di Sant'Agnese PA, Moynes RA, Hiipakka RA, Liao S, Cockett AT et al. The androgen receptor status of neuroendocrine cells in human benign and malignant prostatic tissue. Cancer Res 1993; 53: 1967–1970.
Kadmon D, Thompson TC, Lynch GR, Scardino PT . Elevated plasma chromogranin-A concentrations in prostatic carcinoma. J Urol 1991; 146: 358–361.
di Sant'Agnese PA . Neuroendocrine differentiation in prostatic carcinoma: an update on recent developments. Ann Oncol 2001; 12 (Suppl 2): S135–S140.
Berruti A, Dogliotti L, Mosca A, Bellina M, Mari M, Torta M et al. Circulating neuroendocrine markers in patients with prostate carcinoma. Cancer 2000; 88: 2590–2597.
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.
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.
Grimaldi F, Valotto C, Barbina G, Visentini D, Trianni A, Cerruto MA et al. The possible role of chromogranin A as a prognostic factor in organ-confined prostate cancer. Int J Biol Markers 2006; 21: 229–234.
Ahlegren G, Pedersen K, Lundberg S, Aus G, Hugosson J, Abrahamsson P . Neuroendocrine differentiation is not prognostic of failure after radical prostatectomy but correlates with tumor volume. Urology 2000; 56: 1011–1015.
Lilleby W, Paus E, Skovlund E, Fossa SD . Prognostic value of neuroendocrine serum markers and PSA in irradiated patients with pN0 localized prostate cancer. Prostate 2001; 46: 126–133.
Zitella A, Berruti A, Destefanis P, Mengozzi G, Torta M, Ceruti C et al. Comparison between two commercially available chromogranin A assays in detecting neuroendocrine differentiation in prostate cancer and benign prostate hyperplasia. Clin Chim Acta 2007; 377: 103–107.
Sciarra A, Voria G, Monti S, Mazzone L, Mariotti G, Pozza M et al. Clinical understaging in patients with prostate adenocarcinoma submitted to radical prostatectomy: predictive value of serum chromogranin A. Prostate 2004; 58: 421–428.
Zaky Ahel M, Kovacic K, Kraljic I, Tarle M . Oral estramustine therapy in serum chromogranin A-positive stage D3 prostate cancer patients. Anticancer Res 2001; 21 (2B): 1475–1479.
Cabrespine A, Guy L, Gachon F, Cure H, Chollet P, Bay J-O . Circulating chromogranin A and hormone refractory prostate cancer chemotherapy. J Urol 2006; 175: 1347–1352.
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: 224–230.
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.
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.
Taplin M-E, 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.
Kamiya N, Akakura K, Suzuki H, Isshiki S, Komiya A, Ueda T et al. Pretreatment serum level of neuron specific enolase (NSE) as a prognostic factor in metastatic prostate cancer patients treated with endocrine therapy. Eur Urol 2003; 44: 309–314.
Lilja H . A kallikrein-like serine protease in prostatic fluid cleaves the predominant seminal vesicle protein. J Clin Invest 1985; 76: 1899–1903.
Chapdelaine P, Paradis G, Tremblay RR, Dube JY . High level of expression in the prostate of a human glandular kallikrein mRNA related to prostate-specific antigen. FEBS Lett 1988; 236: 205–208.
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.
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.
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.
Partin AW, Catalona WJ, Finlay JA, Darte C, Tindall DJ, Young CYF et al. Use of human glandular kallikrein 2 for the detection of prostate cancer: preliminary analysis. Urology 1999; 54: 839–845.
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.
Becker C, Piironen T, Pettersson K, Hugosson J, Lilja H . Testing in serum for human glandular kallikrein 2, and free and total prostate specific antigen in biannual screening for prostate cancer. J Urol 2003; 170 (4 Part 1): 1169–1174.
Roobol MJ, Lilja HG, Schroeder FH . Use of total PSA, free PSA, %fPSA, and hK2 measurements to predict occurrence of prostate cancer at biopsy, ERSPC Rotterdam. J Urol, AUA Annual Meeting 2007; 177 (No. 4, Suppl): Abstract 1612.
Haese A, Graefen M, Becker C, Noldus J, Katz J, Cagiannos I et al. The role of human glandular kallikrein 2 for prediction of pathologically organ confined prostate cancer. Prostate 2003; 54: 181–186.
Steuber T, Vickers AJ, Haese A, Becker C, Pettersson K, Chun FK et al. Risk assessment for biochemical recurrence prior to radical prostatectomy: significant enhancement contributed by human glandular kallikrein 2 (hK2) and free prostate specific antigen (PSA) in men with moderate PSA-elevation in serum. Int J Cancer 2006; 118: 1234–1240.
Korets R, Serio AM, Wenske S, Vickers AJ, Vaisanen V, Fleisher M et al. Longitudinal evaluation of molecular PSA isoforms and human glandular kallikrein 2 in predicting biochemical failure following radical prostatectomy. J Urol, AUA Annual Meeting 2007; 177 (No. 4, Suppl): Abstract 1607.
Steuber T, Vickers AJ, Serio AM, Vaisanen V, Haese A, Pettersson K et al. Comparison of free and total forms of serum human kallikrein 2 and prostate-specific antigen for prediction of locally advanced and recurrent prostate cancer. Clin Chem 2007; 53: 233–240.
Evans CP, Elfman F, Parangi S, Conn M, Cunha G, Shuman MA . Inhibition of prostate cancer neovascularization and growth by urokinase-plasminogen activator receptor blockade. Cancer Res 1997; 57: 3594–3599.
Testa JE, Quigley JP . The role of urokinase-type plasminogen activator in aggressive tumor cell behavior. Cancer Metastasis Rev 1990; 9: 353–367.
Van Veldhuizen PJ, Sadasivan R, Cherian R, Wyatt A . Urokinase-type plasminogen activator expression in human prostate carcinomas. Am J Med Sci 1996; 312: 8–11.
Hoosein NM, Boyd DD, Hollas WJ, Mazar A, Henkin J, Chung LW . Involvement of urokinase and its receptor in the invasiveness of human prostatic carcinoma cell lines. Cancer Commun 1991; 3: 255–264.
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.
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.
Milanese G, Gasparri L, Sidenius N, Canonici M, Dellabella M, Galosi AB et al. Evaluation of epidermal growth factor receptor and urokinase-type plasminogen activator receptor in serum of prostate cancer patients. J Urol, AUA Annual Meeting 2007; 177 (No. 4, Suppl):Abstract 1437.
Shariat SF, Roehrborn CG, McConnell JD, Park S, Wheeler TM, Slawin KM . Association of blood levels of components of the urokinase system of plasminogen activation with prostate cancer presence, invasion, progression, and metastasis. J Urol, AUA Annual Meeting 2007; 177 (No. 4, Suppl): Abstract 1433.
Piironen T, Laursen B, Pass J, List K, Gardsvoll H, Ploug M et al. Specific immunoassays for detection of intact and cleaved forms of the urokinase receptor. Clin Chem 2004; 50: 2059–2068.
Piironen T, Haese A, Huland H, Steuber T, Christensen IJ, Brunner N et al. Enhanced discrimination of benign from malignant prostatic disease by selective measurements of cleaved forms of urokinase receptor in serum. Clin Chem 2006; 52: 838–844.
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.
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.
Perry KT, Anthony CT, Case T, Steiner MS . Transforming growth factor beta as a clinical biomarker for prostate cancer. Urology 1997; 49: 151–155.
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 (4A): 2657–2659.
Adler HL, McCurdy MA, Kattan MW, Timme TL, Scardino PT, Thompson TC . Elevated levels of circulating interleukin-6 and transforming growth factor-beta1 in patients with metastatic prostatic carcinoma. J Urol 1999; 161: 182–187.
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.
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.
Sinnreich O, Kratzsch J, Reichenbach A, Glaser C, Huse K, Birkenmeier G . Plasma levels of transforming growth factor-1beta and alpha2-macroglobulin before and after radical prostatectomy: association to clinicopathological parameters. Prostate 2004; 61: 201–208.
Giri D, Ozen M, Ittmann M . Interleukin-6 is an autocrine growth factor in human prostate cancer. Am J Pathol 2001; 159: 2159–2165.
Lee SO, Lou W, Hou M, de Miguel F, Gerber L, Gao AC . Interleukin-6 promotes androgen-independent growth in LNCaP human prostate cancer cells. Clin Cancer Res 2003; 9: 370–376.
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.
George DJ, Halabi S, Shepard TF, Sanford B, Vogelzang NJ, Small EJ et al. The prognostic significance of plasma interleukin-6 levels in patients with metastatic hormone-refractory prostate cancer: results from cancer and leukemia group B 9480. Clin Cancer Res 2005; 11: 1815–1820.
Xu T, Chen X, Wang XF, Hou SK, Zhu JC, Zhang XD et al. Study of PSA, PSMA and hK2 mRNA in peripheral blood of prostate cancer patients and its clinical implications. Beijing Da Xue Xue Bao 2004; 36: 164–168.
Murphy GP, Kenny GM, Ragde H, Wolfert RL, Boynton AL, Holmes EH et al. Measurement of serum prostate-specific membrane antigen, a new prognostic marker for prostate cancer. Urology 1998; 51 (5A Suppl): 89–97.
Marchal C, Redondo M, Padilla M, Caballero J, Rodrigo I, Garcia J et al. Expression of prostate specific membrane antigen (PSMA) in prostatic adenocarcinoma and prostatic intraepithelial neoplasia. Histol Histopathol 2004; 19: 715–718.
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.
Chu DC, Chuang CK, Liou YF, Tzou RD, Lee HC, Sun CF . The use of real-time quantitative PCR to detect circulating prostate-specific membrane antigen mRNA in patients with prostate carcinoma. Ann NY Acad Sci 2004; 1022: 157–162.
Ellis WJ, Vessella RL, Corey E, Arfman EW, Oswin MM, Melchior S et al. The value of a reverse transcriptase polymerase chain reaction assay in preoperative staging and followup of patients with prostate cancer. J Urol 1998; 159: 1134–1138.
Grasso YZ, Gupta MK, Levin HS, Zippe CD, Klein EA . Combined nested RT-PCR assay for prostate-specific antigen and prostate-specific membrane antigen in prostate cancer patients: correlation with pathological stage. Cancer Res 1998; 58: 1456–1459.
Thomas J, Gupta M, Grasso Y, Reddy CA, Heston WD, Zippe C et al. Preoperative combined nested reverse transcriptase polymerase chain reaction for prostate-specific antigen and prostate-specific membrane antigen does not correlate with pathologic stage or biochemical failure in patients with localized prostate cancer undergoing radical prostatectomy. J Clin Oncol 2002; 20: 3213–3218.
Xiao Z, Adam BL, Cazares LH, Clements MA, Davis JW, Schellhammer PF et al. Quantitation of serum prostate-specific membrane antigen by a novel protein biochip immunoassay discriminates benign from malignant prostate disease. Cancer Res 2001; 61: 6029–6033.
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.
Gu Z, Thomas G, Yamashiro J, Shintaku IP, Dorey F, Raitano A et al. Prostate stem cell antigen (PSCA) expression increases with high Gleason score, advanced stage and bone metastasis in prostate cancer. Oncogene 2000; 19: 1288–1296.
Han K-R, Seligson DB, Liu X, Horvath S, Shintaku PI, Thomas GV et al. Prostate stem cell antigen expression is associated with Gleason score, seminal vesicle invasion and capsular invasion in prostate cancer. J Urol 2004; 171: 1117–1121.
Lam JS, Yamashiro J, Shintaku IP, Vessella RL, Jenkins RB, Horvath S et al. Prostate stem cell antigen is overexpressed in prostate cancer metastases. Clin Cancer Res 2005; 11: 2591–2596.
Zhigang Z, Wenlu S . Complete androgen ablation suppresses prostate stem cell antigen (PSCA) mRNA expression in human prostate carcinoma. Prostate 2005; 65: 299–305.
Zhigang Z, Wenlu S . External beam radiotherapy (EBRT) suppressed prostate stem cell antigen (PSCA) mRNA expression in clinically localized prostate cancer. Prostate 2007; 67: 653–660.
Hara N, Kasahara T, Kawasaki T, Bilim V, Obara K, Takahashi K et al. Reverse transcription-polymerase chain reaction detection of prostate-specific antigen, prostate-specific membrane antigen, and prostate stem cell antigen in one milliliter of peripheral blood: value for the staging of prostate cancer. Clin Cancer Res 2002; 8: 1794–1799.
Kuefer R, Varambally S, Zhou M, Lucas PC, Loeffler M, Wolter H et al. Alpha-methylacyl-CoA racemase: expression levels of this novel cancer biomarker depend on tumor differentiation. Am J Pathol 2002; 161: 841–848.
Zha S, Ferdinandusse S, Denis S, Wanders RJ, Ewing CM, Luo J et al. Alpha-methylacyl-CoA racemase as an androgen-independent growth modifier in prostate cancer. Cancer Res 2003; 63: 7365–7376.
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.
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.
Jiang Z, Wu CL, Woda BA, Dresser K, Xu J, Fanger GR et al. P504S/alpha-methylacyl-CoA racemase: a useful marker for diagnosis of small foci of prostatic carcinoma on needle biopsy. Am J Surg Pathol 2002; 26: 1169–1174.
Zehentner BK, Secrist H, Zhang X, Hayes DC, Ostenson R, Goodman G et al. Detection of alpha-methylacyl-coenzyme-A racemase transcripts in blood and urine samples of prostate cancer patients. Mol Diagn Ther 2006; 10: 397–403.
Cardillo MR, Gentile V, Ceccariello A, Giacomelli L, Messinetti S, Di Silverio F . Can p503s, p504s and p510s gene expression in peripheral-blood be useful as a marker of prostatic cancer? BMC Cancer 2005; 5: 111.
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.
Jiang Z, Fanger GR, Woda BA, Banner BF, Algate P, Dresser K et al. Expression of alpha-methylacyl-CoA racemase (P504s) in various malignant neoplasms and normal tissues: a study of 761 cases. Hum Pathol 2003; 34: 792–796.
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.
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.
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.
Hansel DE, DeMarzo AM, Platz EA, Jadallah S, Hicks J, Epstein JI et al. Early prostate cancer antigen expression in predicting presence of prostate cancer in men with histologically negative biopsies. J Urol 2007; 177: 1736–1740.
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.
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.
Leman ES, Cannon GW, Trock BJ, Sokoll LJ, Chan DW, Mangold LA et al. Further analysis of serum based EPCA-2 as a specific prostate cancer associated biomarker. J Urol, AUA Annual Meeting 2007; 177 (No. 4, Suppl): Abstract 1431.
Bastian PJ, Yegnasubramanian S, Palapattu GS, Rogers CG, Lin X, De Marzo AM et al. Molecular biomarker in prostate cancer: the role of CpG island hypermethylation. Eur Urol 2004; 46: 698–708.
Lin X, Tascilar M, Lee WH, Vles WJ, Lee BH, Veeraswamy R et al. GSTP1 CpG island hypermethylation is responsible for the absence of GSTP1 expression in human prostate cancer cells. Am J Pathol 2001; 159: 1815–1826.
Nelson WG, De Marzo AM, DeWeese TL . The molecular pathogenesis of prostate cancer: implications for prostate cancer prevention. Urology 2001; 57 (4 Suppl 1): 39–45.
Nakayama M, Bennett CJ, Hicks JL, Epstein JI, Platz EA, Nelson WG et al. Hypermethylation of the human glutathione S-transferase-pi gene (GSTP1) CpG island is present in a subset of proliferative inflammatory atrophy lesions but not in normal or hyperplastic epithelium of the prostate: a detailed study using laser-capture microdissection. Am J Pathol 2003; 163: 923–933.
Rosenbaum E, Hoque MO, Cohen Y, Zahurak M, Eisenberger MA, Epstein JI et al. Promoter hypermethylation as an independent prognostic factor for relapse in patients with prostate cancer following radical prostatectomy. Clin Cancer Res 2005; 11: 8321–8325.
Bastian PJ, Ellinger J, Wellmann A, Wernert N, Heukamp LC, Muller SC et al. Diagnostic and prognostic information in prostate cancer with the help of a small set of hypermethylated gene loci. Clin Cancer Res 2005; 11: 4097–4106.
Jeronimo C, Henrique R, Hoque MO, Mambo E, Ribeiro FR, Varzim G et al. A quantitative promoter methylation profile of prostate cancer. Clin Cancer Res 2004; 10: 8472–8478.
Goessl C, Muller M, Miller K . Methylation-specific PCR (MSP) for detection of tumour DNA in the blood plasma and serum of patients with prostate cancer. Prostate Cancer Prostatic Dis 2000; 3 (S1): S17.
Jeronimo C, Usadel H, Henrique R, Silva C, Oliveira J, Lopes C et al. Quantitative GSTP1 hypermethylation in bodily fluids of patients with prostate cancer. Urology 2002; 60: 1131–1135.
Bastian PJ, Palapattu GS, Lin X, Yegnasubramanian S, Mangold LA, Trock B et al. Preoperative serum DNA GSTP1 CpG island hypermethylation and the risk of early prostate-specific antigen recurrence following radical prostatectomy. Clin Cancer Res 2005; 11: 4037–4043.
Goessl C, Muller M, Heicappell R, Krause H, Miller K . DNA-based detection of prostate cancer in blood, urine, and ejaculates. Ann NY Acad Sci 2001; 945: 51–58.
Yang LY, Babaian RJ, Fritsche HA . A novel serum DNA based assay to enhance the detection of prostate cancer. J Urol, AUA Annual Meeting 2007; 177 (No. 4, Suppl): Abstract 1710.
Bastian PJ, Palapattu GS, Yegnasubramanian S, Lin X, Rogers CG, Mangold LA et al. CpG island hypermethylation profile in preoperative serum of men with clinically localized and hormone-refractory metastatic prostate cancer. J Urol, AUA Annual Meeting 2007; 177 (No. 4, Suppl): Abstract 655.
Noble RL . The development of prostatic adenocarcinoma in Nb rats following prolonged sex hormone administration. Cancer Res 1977; 37: 1929–1933.
Wu CP, Gu FL . The prostate in eunuchs. Prog Clin Biol Res 1991; 370: 249–255.
Glantz GM . Cirrhosis and carcinoma of the prostate gland. J Urol 1964; 91: 291–293.
Dorgan JF, Albanes D, Virtamo J, Heinonen OP, Chandler DW, Galmarini M et al. Relationships of serum androgens and estrogens to prostate cancer risk: results from a prospective study in Finland. Cancer Epidemiol Biomarkers Prev 1998; 7: 1069–1074.
Mohr BA, Feldman HA, Kalish LA, Longcope C, McKinlay JB . Are serum hormones associated with the risk of prostate cancer? Prospective results from the Massachusetts Male Aging Study. Urology 2001; 57: 930–935.
Chen C, Weiss NS, Stanczyk FZ, Lewis SK, DiTommaso D, Etzioni R et al. Endogenous sex hormones and prostate cancer risk: a case–control study nested within the Carotene and Retinol Efficacy Trial. Cancer Epidemiol Biomarkers Prev 2003; 12: 1410–1416.
Stattin P, Lumme S, Tenkanen L, Alfthan H, Jellum E, Hallmans G et al. High levels of circulating testosterone are not associated with increased prostate cancer risk: a pooled prospective study. Int J Cancer 2004; 108: 418–424.
Severi G, Morris HA, MacInnis RJ, English DR, Tilley W, Hopper JL et al. Circulating steroid hormones and the risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 2006; 15: 86–91.
Hoffman MA, DeWolf WC, Morgentaler A . Is low serum free testosterone a marker for high grade prostate cancer? J Urol 2000; 163: 824–827.
Schatzl G, Madersbacher S, Thurridl T, Waldmuller J, Kramer G, Haitel A et al. High-grade prostate cancer is associated with low serum testosterone levels. Prostate 2001; 47: 52–58.
Han M, Partin AW, Pound CR, Epstein JI, Walsh PC . Long-term biochemical disease-free and cancer-specific survival following anatomic radical retropubic prostatectomy. The 15-year Johns Hopkins experience. Urol Clin North Am 2001; 28: 555–565.
Isom-Batz G, Bianco Jr FJ, Kattan MW, Mulhall JP, Lilja H, Eastham JA . Testosterone as a predictor of pathological stage in clinically localized prostate cancer. J Urol 2005; 173: 1935–1937.
Yano M, Imamoto T, Suzuki H, Fukasawa S, Kojima S, Komiya A et al. The clinical potential of pretreatment serum testosterone level to improve the efficiency of prostate cancer screening. Eur Urol 2007; 51: 375–380.
Yamamoto S, Yonese J, Kawakami S, Ohkubo Y, Tatokoro M, Komai Y et al. Preoperative serum testosterone level as an independent predictor of treatment failure following radical prostatectomy. Eur Urol 2007; 52: 696–701.
Lane BR, Stephenson AJ, Reuther AM, Kattan MW, Magi-Galluzzi C, Zhou M et al. Low pretreatment total testosterone levels are associated with a predominance of pattern for prostate cancer at prostatectomy and risk of biochemical recurrence. J Urol, AUA Annual Meeting 2007; 177 (No. 4, Suppl): Abstract 1617.
Gann PH, Hennekens CH, Ma J, Longcope C, Stampfer MJ . Prospective study of sex hormone levels and risk of prostate cancer. J Natl Cancer Inst 1996; 88: 1118–1126.
Salonia A, Briganti A, Gallina A, Zanni G, Sacca A, Capitanio U et al. Sex hormone binding globulin: a novel marker for predicting lymph node metastases in patients with clinically localized prostate cancer undergoing an extended pelvic lymph node dissection. J Urol, AUA Annual Meeting 2007; 177 (No. 4, Suppl): Abstract 1616.
Salonia A, Gallina A, Briganti A, Zanni G, Capitanio U, Sacca A et al. Sex hormone binding globulin is a significant predictor of extra capsular extension in patients undergoing radical retropubic prostatectomy. J Urol, AUA Annual Meeting 2007; 177 (No. 4, Suppl): Abstract 1615.
Tahir SA, Frolov A, Hayes TG, Mims MP, Miles BJ, Lerner SP et al. Preoperative serum caveolin-1 as a prognostic marker for recurrence in a radical prostatectomy cohort. Clin Cancer Res 2006; 12: 4872–4875.
Kuefer R, Hofer MD, Zorn CS, Engel O, Volkmer BG, Juarez-Brito MA et al. Assessment of a fragment of e-cadherin as a serum biomarker with predictive value for prostate cancer. Br J Cancer 2005; 92: 2018–2023.
Assikis VJ, Do KA, Wen S, Wang X, Cho-Vega JH, Brisbay S et al. Clinical and biomarker correlates of androgen-independent, locally aggressive prostate cancer with limited metastatic potential. Clin Cancer Res 2004; 10: 6770–6778.
Baker T, Tickle S, Wasan H, Docherty A, Isenberg D, Waxman J . Serum metalloproteinases and their inhibitors: markers for malignant potential. Br J Cancer 1994; 70: 506–512.
Naughton M, Picus J, Zhu X, Catalona WJ, Vollmer RT, Humphrey PA . Scatter factor-hepatocyte growth factor elevation in the serum of patients with prostate cancer. J Urol 2001; 165: 1325–1328.
Stephan C, Xu C, Brown DA, Breit SN, Michael A, Nakamura T et al. Three new serum markers for prostate cancer detection within a percent free PSA-based artificial neural network. Prostate 2006; 66: 651–659.
Yashi M, Muraishi O, Kobayashi Y, Tokue A, Nanjo H . Elevated serum progastrin-releasing peptide (31–98) in metastatic and androgen-independent prostate cancer patients. Prostate 2002; 51: 84–97.
Hlavaty JJ, Partin AW, Shue MJ, Mangold LA, Derby J, Javier T et al. Identification and preliminary clinical evaluation of a 50.8-kDa serum marker for prostate cancer. Urology 2003; 61: 1261–1265.
Khosravi J, Diamandi A, Mistry J, Scorilas A . Insulin-like growth factor I (IGF-I) and IGF-binding protein-3 in benign prostatic hyperplasia and prostate cancer. J Clin Endocrinol Metab 2001; 86: 694–699.
Stattin P, Stenman UH, Riboli E, Hallmans G, Kaaks R . Ratios of IGF-I, IGF binding protein-3, and prostate-specific antigen in prostate cancer detection. J Clin Endocrinol Metab 2001; 86: 5745–5748.
Trojan L, Bode C, Weiss C, Mayer D, Grobholz R, Alken P et al. IGF-II serum levels increase discrimination between benign prostatic hyperplasia and prostate cancer and improve the predictive value of PSA in clinical staging. Eur Urol 2006; 49: 286–292; discussion 292.
Stattin P, Soderberg S, Hallmans G, Bylund A, Kaaks R, Stenman UH et al. Leptin is associated with increased prostate cancer risk: a nested case-referent study. J Clin Endocrinol Metab 2001; 86: 1341–1345.
O'Connor JC, Farach-Carson MC, Schneider CJ, Carson DD . Coculture with prostate cancer cells alters endoglin expression and attenuates transforming growth factor-beta signaling in reactive bone marrow stromal cells. Mol Cancer Res 2007; 5: 585–603.
Karam JA, Svatek RS, Jenkins A, Roehrborn CG, Koeneman KS, Slawin KM et al. Pre-operative plasma endoglin levels predict metastasis to lymph nodes and disease progression in patients treated with radical prostatectomy. J Urol, AUA Annual Meeting 2007; 177 (No. 4, Suppl): Abstract 1426.
Okegawa T, Kinjo M, Nutahara K, Higashihara E . Pretreatment serum level of HER2/nue as a prognostic factor in metastatic prostate cancer patients about to undergo endocrine therapy. Int J Urol 2006; 13: 1197–1201.
Landers KA, Burger MJ, Tebay MA, Purdie DM, Scells B, Samaratunga H et al. Use of multiple biomarkers for a molecular diagnosis of prostate cancer. Int J Cancer 2005; 114: 950–956.
Botchkina GI, Kim RH, Botchkina IL, Kirshenbaum A, Frischer Z, Adler HL . Noninvasive detection of prostate cancer by quantitative analysis of telomerase activity. Clin Cancer Res 2005; 11: 3243–3249.
Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG et al. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 2002; 419: 624–629.
Grignon DJ, Caplan R, Sarkar FH, Lawton CA, Hammond EH, Pilepich MV et al. p53 status and prognosis of locally advanced prostatic adenocarcinoma: a study based on RTOG 8610. J Natl Cancer Inst 1997; 89: 158–165.
Shafer MW, Mangold L, Partin AW, Haab BB . Antibody array profiling reveals serum TSP-1 as a marker to distinguish benign from malignant prostatic disease. Prostate 2007; 67: 255–267.
Minelli A, Ronquist G, Carlsson L, Mearini E, Nilsson O, Larsson A . Antiprostasome antibody titres in benign and malignant prostate disease. Anticancer Res 2005; 25 (6C): 4399–4402.
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.
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.
Petricoin III EF, Ornstein DK, Paweletz CP, Ardekani A, Hackett PS, Hitt BA et al. Serum proteomic patterns for detection of prostate cancer. J Natl Cancer Inst 2002; 94: 1576–1578.
Mann M, Hendrickson RC, Pandey A . Analysis of proteins and proteomes by mass spectrometry. Annu Rev Biochem 2001; 70: 437–473.
Zheng Y, Xu Y, Ye B, Lei J, Weinstein MH, O'Leary MP et al. Prostate carcinoma tissue proteomics for biomarker discovery. Cancer 2003; 98: 2576–2582.
Flaig TW, Nordeen SK, Lucia MS, Harrison GS, Glode LM . Conference report and review: current status of biomarkers potentially associated with prostate cancer outcomes. J Urol 2007; 177: 1229–1237.
Wright Jr GL, Cazares LH, Leung SM, Nasim S, Adam BL, Yip TT et al. Proteinchip(R) surface enhanced laser desorption/ionization (SELDI) mass spectrometry: a novel protein biochip technology for detection of prostate cancer biomarkers in complex protein mixtures. Prostate Cancer Prostatic Dis 1999; 2 (5/6): 264–276.
Adam BL, Qu Y, Davis JW, Ward MD, Clements MA, Cazares LH et al. Serum protein fingerprinting coupled with a pattern-matching algorithm distinguishes prostate cancer from benign prostate hyperplasia and healthy men. Cancer Res 2002; 62: 3609–3614.
Banez LL, Prasanna P, Sun L, Ali A, Zou Z, Adam BL et al. Diagnostic potential of serum proteomic patterns in prostate cancer. J Urol 2003; 170 (2 Part 1): 442–446.
Qu Y, Adam BL, Yasui Y, Ward MD, Cazares LH, Schellhammer PF et al. Boosted decision tree analysis of surface-enhanced laser desorption/ionization mass spectral serum profiles discriminates prostate cancer from noncancer patients. Clin Chem 2002; 48: 1835–1843.
Pan YZ, Xiao XY, Zhao D, Zhang L, Ji GY, Li Y et al. Application of surface-enhanced laser desorption/ionization time-of-flight-based serum proteomic array technique for the early diagnosis of prostate cancer. Asian J Androl 2006; 8: 45–51.
Ornstein DK, Rayford W, Fusaro VA, Conrads TP, Ross SJ, Hitt BA 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 (4 Part 1): 1302–1305.
van Gils MP, Stenman UH, Schalken JA, Schroder FH, Luider TM, Lilja H et al. Innovations in serum and urine markers in prostate cancer current European research in the P-Mark project. Eur Urol 2005; 48: 1031–1041.
About this article
Cite this article
Ramírez, M., Nelson, E. & Evans, C. Beyond prostate-specific antigen: alternate serum markers. Prostate Cancer Prostatic Dis 11, 216–229 (2008). https://doi.org/10.1038/pcan.2008.2
- AMACR autoantibodies
- GSTP1 hypermethylation
Indian Journal of Clinical Biochemistry (2013)
Inverse association of p16INK4a and p14ARF methylation of the CDKN2a locus in different Gleason scores of prostate cancer
Prostate Cancer and Prostatic Diseases (2011)
Asian Journal of Andrology (2009)
Asian Journal of Andrology (2009)