Prostat-Specific Antigen: Biochemical, Molecular-Biological, and Analytical Aspects

Yana Sydyakina, Anastasia Sivakova, Anatolii Komar, Alexander Galkin


Background. Prostate cancer incidence in the world and in Ukraine is steadily increasing due to the difficulties of early diagnosis and late detection of the disease. For a diagnosis of prostate cancer tests for specific blood markers detection in the human blood serum are used, first of all, tests for prostate-specific antigen (PSA) detection – glycoprotein with enzymatic activity, which is secreted by the cells of the prostate. Detection of PSA has a number of analytical features due to biochemical and serological properties of some PSA forms, which, in turn, results in the continuous improvement of methods for its detection.

Objective. Analysis of modern scientific data on the biochemical and molecular biological properties of PSA, as well as methods for its measurement in human biological fluids.

Methods. The literature data on the molecular bases of synthesis, biochemical features and the role of PSA in the human body are systematized and analyzed, modern data on methods for PSA measurement are analyzed critically.

Results. PSA has peculiarities of the biosynthesis and post-translational modifications, which directly affect its functions in the human body and the activity of the serum marker in prostate cancer diagnostics. Modern methods of analysis allow to deteсt most of the forms of PSA with high sensitivity. The most common methods of clinical laboratory diagnosis are enzyme immunoassay and immunochromatography.

Conclusions. Analysis of the literature has shown that in the future further studies on the role of PSA for other than the prostate organs of a person will be carried on, as well as the development and improvement of tests for prostate cancer diagnostic and detection of other oncological diseases with the use of PSA, for example, breast cancer, will take place.


Prostate-specific antigen; Prostate cancer; Human kallikrein 3; Serine proteinase; Prostate-specific antigen detection methods


Shcherbina O, Sakalo V, Kovalev M, Chernenko O. Prostate cancer: diagnostics and monitoring. Oncology. 2006;8(4):322-6.

Sasaki T, Sugimura Y. The importance of time to prostate-specific antigen (PSA) nadir after primary androgen deprivation therapy in hormone-naïve prostate cancer patients. J Clin Med. 2018;7(12):1-9. DOI: 10.3390/jcm7120565

Fedorenko Z, Gajsenko A, Gulak L. Incidence, mortality, indicators of the oncology service activity. Byuleten Nacionalnogo Kancer-Reyestru Ukrayiny. 2011;12:116.

Semeniv І, Kalenska O, Kuryk O. Immunohistochemical diagnostics of precancerous diseases and prostate cancer. Sci J Ministry of Health of Ukraine. 2013;2:72-8.

Sergeeva N, Mazo E, Grygorev M, Makarova L, Soloveva E. Complex prostatic specific antigen and its diagnostic significance. Laboratornaya Medycyna. 2005;7:55-8.

Nordström T, Akre O, Aly M, Grönberg H, Eklund M. Prostate-specific antigen (PSA) density in the diagnostic algorithm of prostate cancer. Prostate Cancer Prostatic Dis. 2018;21(1):57-63. DOI: 10.1038/s41391-017-0024-7

Tailor P, Kodeboyina S, Bai S, Patel N, Sharma S, Ratnani A, et al. Diagnostic and prognostic biomarker potential of kallikrein family genes in different cancer types. Oncotarget. 2018;9(25):17876-88. DOI: 10.18632/oncotarget.24947

Leis-Filho AF, Fonseca-Alves CE. Anatomy, histology, and physiology of the canine prostate gland. In: Veterinary Anatomy and Physiology. IntechOpen; 2019. DOI: 10.5772/intechopen.81410

Loessner D, Goettig P, Preis S, Felber J, Bronger H, Clements J, et al. Kallikrein-related peptidases represent attractive therapeutic targets for ovarian cancer. Expert Opin Ther Targets. 2018;22(9):745-63. DOI: 10.1080/14728222.2018.1512587

Sävblom C. The Kallikrein-related peptidases hK2 and PSA with emphasis on genetic variation, secretion, and sperm motility [Internet]. 2019 [cited 2019 Apr 9]. Available from:

Lawrence M, Lai J, Clements J. Kallikreins on steroids: structure, function, and hormonal regulation of prostate-specific antigen and the extended kallikrein locus. Endocrine Rev. 2010;31(4):407-46. DOI: 10.1210/er.2009-0034

Pérez-Ibave D, Burciaga-Flores C, Elizondo-Riojas M. Prostate-specific antigen (PSA) as a possible biomarker in non-prostatic cancer: a review. Cancer Epidemiol. 2018;54:48-55. DOI: 10.1016/j.canep.2018.03.009

Clements J, Hooper J, Dong Y, Harvey T. The expanded human kallikrein (KLK) gene family: genomic organisation, tissue-specific expression and potential functions. Biol Chem. 2001;382(1):5-14. DOI: 10.1515/BC.2001.002

Diamandis E. Prostate-specific antigen: its usefulness in clinical medicine. Trends Endocrinol Metab. 1998;9(8):310-6. DOI: 10.1016/S1043-2760(98)00082-4

Riegman PHJ. Prostate specific antigen: gene structure and regulation of expression [dissertation]. Rotterdam: Erasmus University Rotterdam; 1992. 136 p.

Kim J, Coetzee G. Prostate specific antigen gene regulation by androgen receptor. J Cell Biochem. 2004;93(2):233-41. DOI: 10.1002/jcb.20228

Zhu Y, Cai L, You X, Cordero J, Huang Y, Imperato-McGinley J. Androgen-induced prostate-specific antigen gene expres­sion is mediated via dihydrotestosterone in LNCaP cells. J Androl. 2003;24(5):681-7. DOI: 10.1002/j.1939-4640.2003.tb02727.x

Liu X, Choi R, Jawad S, Arnold J. Androgen-induced PSA expression requires not only activation of AR but also endogenous IGF-I or IGF-I/PI3K/Akt signaling in human prostate cancer epithelial cells. Prostate. 2010;71(7):766-77. DOI: 10.1002/pros.21293

Mohler J, Tindall D. Androgen action in prostate cancer. New York: Springer-Verlag New York; 2009. 826 p.

Seaton A, Scullin P, Maxwell PJ, Wilson C, Pettigrew J, Gallagher R, et al. Interleukin-8 signaling promotes androgen-independent proliferation of prostate cancer cells via induction of androgen receptor expression and activation. Carcinogenesis. 2008;29(6):1148-56. DOI: 10.1093/carcin/bgn109

Golias C, Iliadis I, Peschos D, Charalabopoulos K. Amplification and co-regulators of androgen receptor gene in prostate cancer. Exp Oncol. 2009;31(1):3-8.

Sadar MD. Androgen-independent induction of prostate-specific antigen gene expression via cross-talk between the androgen receptor and protein kinase A signal transduction pathways. J Biol Chem. 1999;274(12):7777-83. DOI: 10.1074/jbc.274.12.7777

Chang C. Prostate cancer: basic mechanisms and therapeutic approaches. World Scientific; 2005. 429 p.

Dixon SC, Knopf KB, Figg WD. The control of prostate-specific antigen expression and gene regulation by pharmacological agents. Pharmacol Rev. 2001;53(1):73-91.

Gurova KV, Roklin OW, Krivokrysenko VI, Chumakov PM, Cohen MB, Feinstein E, et al. Expression of prostate specific antigen (PSA) is negatively regulated by p53. Oncogene. 2002;21(1):153-7. DOI: 10.1038/sj.onc.1205001

Chanan-Khan AAA. Immunomodulating drugs for the treatment of cancer. Lippincott Williams & Wilkins; 2012. 312 p.

Marone G. Angiogenesis, lymphangiogenesis and clinical implications. Basel: Karger; 2014. 232 p.

Bronchud MH. Principles of molecular oncology. 2nd ed. Humana Press Incorporated; 2004. 420 p.

Horti J, Dixon SC, Logothetis CJ, Guo Y, Reed E, Figg WD. Increased transcriptional activity of prostate-specific antigen in the presence of TNP-470, an angiogenesis inhibitor. British J Cancer. 1999;79(9/10):1588-93. DOI: 10.1038/sj.bjc.6690253

Rini BL, Weinberg V, Bok R, Small EJ. Prostate-specific antigen kinetics as a measure of the biologic effect of granulocyte-macrophage colony-stimulating factor in patients with serologic progression of prostate cancer. J Clin Oncol. 2003;21(1):99-105. DOI: 10.1200/JCO.2003.04.163

Diamandis EP. Tumor markers: physiology, pathobiology, technology, and clinical applications. Washington: AACC Press; 2002. 541 p.

Trump DL, Aragon-Ching JB. Vitamin D in prostate cancer. Asian J Androl. 2018;20(3):244-52. DOI: 10.4103/aja.aja_14_18

Shahvazi S, Soltani S, Ahmadi SM, de Souza RJ, Salehi-Abargouei A. The effect of vitamin D supplementation on prostate cancer: a systematic review and meta-analysis of clinical trials. Horm Metab Res. 2019;51(1):11-21. DOI: 10.1055/a-0774-8809

Senderowicz AM, Reid R, Headlee D, Abornathy T, Horti J, Lush RM, et al. A phase II trial of gallium nitrate in patients with androgen-metastaticprostate cancer. Urol Int. 1999;63(2):120-5. DOI: 10.1159/000030430

Spitz A, Young JM, Larsen L, Mattia-Goldberg C, Donnelly J, Chwalisz K. Efficacy and safety of leuprolide acetate 6-month depot for suppression of testosterone in patients with prostate cancer. Prostate Cancer Prostatic Dis. 2012;15(1):93-9. DOI: 10.1038/pcan.2011.50

Kyprianou N. Molecular exploitation of apoptosis pathways in prostate cancer. London: Imperial College Press; 2012. 217 p.

Liu G, Gandara DR, Lara PNJ, Raghavan D, Doroshow JH, Twardowski P, et al. A phase II trial of Flavopiridol (NSC #649890) in patients with previously untreated metastatic androgen-independent prostate cancer. Clin Cancer Res. 2004;10(3):924-8. DOI: 10.1158/1078-0432.CCR-03-0050

Pushkar DY, Govorov AV, Sidorenkov AV, Prilepskaya EA, Kovyilina MV. Early diagnosis of prostate cancer. Moscow: ABC-press; 2015. 54 р.

Vermassen T, Speeckaert MM, Lumen N, Rottey S, Delanghe JR. Glycosylation of prostate specific antigen and its potential diagnostic applications. Clin Chim Acta. 2012;413(19-20):1500-5. DOI: 10.1016/j.cca.2012.06.007

Drake RR, Jones EE, Powers TW, Nyalwidhe JO. Chapter ten – altered glycosylation in prostate cancer. Adv Cancer Res. 2015;126:345-82. DOI: 10.1016/bs.acr.2014.12.001

Okada T, Sato Y, Kobayashi N, Sumida K, Satomura S, Matsuura S, et al. Structural characteristics of the N-glycans of two isoforms of prostate-specific antigens purified from human semina. Biochim Biophys Acta. 2001;1525(1-2):149-60. DOI: 10.1016/S0304-4165(00)00182-3

Hatakeyama S, Yoneyama T, Tobisawa Y, Ohyama C. Recent progress and perspectives on prostate cancer biomarkers. Int J Clin Oncol. 2017;22:214. DOI: 10.1007/s10147-016-1049-y

Llop E, Ferrer-Batallé M, Barrabés S, Guerrero PE, Ramírez M, Saldova R, et al. Improvement of prostate cancer diagnosis by detecting PSA glycosylation-specific changes: erratum. Theranostics. 2018;8(3):746-8. DOI: 10.7150/thno.23906

Kammeijer GSM, Nouta J, de la Rosette JJMCH, de Reijke TM, Wuhrer M. An in-depth glycosylation assay for urinary prostate-specific antigen. Anal Chem. 2018;90(7):4414-21. DOI: 10.1021/acs.analchem.7b04281

Heidegger I, Klocker H, Pichler R, Pircher A, Prokop W, Steiner E, et al. ProPSA and the Prostate Health Index as predictive markers for aggressiveness in low-risk prostate cancer—results from an international multicenter study. Prostate Cancer Prostatic Dis. 2017;20(3):271-5. DOI: 10.1038/pcan.2017.3

Peyromaure M, Fulla Y, Debré B, Dinh-Xuan AT. Pro PSA: a "pro cancer" form of PSA? Med Hypotheses. 2005; 64(1):92-5. DOI: 10.1016/j.mehy.2004.06.006

Balk SP, Ko YJ, Bubley GJ. Biology of prostate-specific antigen. J Clin Oncol. 2003;21(2):383-91. DOI: 10.1200/JCO.2003.02.083

Mikolajczyk SD, Rittenhouse HG. Pro PSA: a more cancer specific form of prostate specific antigen for the early detection of prostate cancer. Keio J Med. 2003;52(2):86-91. DOI: 10.2302/kjm.52.86

Spiess PE. Prostate cancer - diagnostic and therapeutic advances. Rijeka: InTech; 2011. 378 p.

Tosoian JJ, Loeb S, Feng Z, Isharwal S, Landis P, Elliot DJ, et al. Association of [-2]proPSA with biopsy reclassification during active surveillance for prostate cancer. J Urol. 2012;188(4):1131-6. DOI: 10.1016/j.juro.2012.06.009

Sidorenkov V, Govorov AV, Sadchenko AV, Pushkar DYu. Diagnostic value of [-2]proPSA and PHI index (review of literature). Onkourologiya. 2014;10(4):87-95.

Semjonow A, Köpke T, Eltze E, Pepping-Schefers B, Bürgel H, Darte C. Pre-analytical in-vitro stability of [-2]proPSA in blood and serum. Clin Biochem. 2010;43(10-11):926-8. DOI: 10.1016/j.clinbiochem.2010.04.062

Vukovic I, Djordjevic D, Bojanic N, Babic U, Soldatovic I. Predictive value of [-2]propsa (p2psa) and its derivatives for the prostate cancer detection in the 2.0 to 10.0ng/mL PSA range. Int Braz J Urol. 2017;43(1):48-56. DOI: 10.1590/S1677-5538.IBJU.2016.0256

Solovov VA. Biology of prostate specific antigen and its role in the pathogenesis of prostate cancer. Vestnik SamGU. 2005;5:200-8.

Prcic A, Begic E, Hiros A. Actual contribution of free to total PSA ratio in prostate diseases differentiation. Med Arch. 2016;70(4):288. DOI: 10.5455/medarh.2016.70.288-292

Zhu L, Jäämaa S, Hällström TMA, Laiho M, Sankila A, Nordling S, et al. PSA forms complexes with α1-antichymotrypsin in prostate. Prostate. 2012;73(2):219-26. DOI: 10.1002/pros.22560

Kostova MB, Brennen WN, Lopez D, Anthony L, Wang H, Platz E, et al. PSA-alpha-2-macroglobulin complex is enzymatically active in the serum of patients with advanced prostate cancer and can degrade circulating peptide hormones. Prostate. 2018;78(11):819-29. DOI: 10.1002/pros.23539

Patel D, Feng T, Simon R, Howard L, Vidal A, Moreira D, et al. PSA predicts development of incident lower urinary tract symptoms: results from the REDUCE study. Prostate Cancer Prostatic Dis. 2018;21(2):238-44. DOI: 10.1038/s41391-018-0044-y

Corey E, Wegner SK, Corey MJ, Vessella RL. Prostate-specific antigen: characterization of epitopes by synthetic peptide mapping and inhibition studies. Clin Chem. 1997;43(4):575-84.

Konovalova EV. Development of quantitative analysis of prostate cancer serological markers on hydrogel microchips [dissertation]. Moscow: Engelhardt Institute of Molecular Biology of Russian Academy of Sciences; 2006. 23 p.

Ménez R, Michel S, Muller B, Bossus M, Ducancel F, Jolivet-Reynaud C, et al. Crystal structure of a ternary complex between human prostate-specific antigen, its substrate acyl intermediate and an activating antibody. J Mol Biol. 2008;376(4):1021-33. DOI: 10.1016/j.jmb.2007.11.052

Chissova VI, Daryalovoy SL. Clinical guidelines. Oncology. Moscow: GEOTAR-Media; 2006. 720 p.

Lilja H. Structure, function, and regulation of the enzyme activity of prostate-specific antigen. World J Urol. 1993;11(4).

Sergeeva NS, Marshutina NV, Solohina MP, Alentov II, Parilova NK, Zenkina EV, et al. Modern conceptions of serological tumor markers and their role in oncology. Uspehi Molekulyarnoy Onkologii. 2014;1:69-80.

Smolyakova RM. Biomolecular criteria for diagnostics and predictio of prostate cancer. Ekologicheskiy Vestnik. 2017;2:80-6.

Jalalvand A. Fabrication of a novel and ultrasensitive label-free electrochemical aptasensor for detection of biomarker prostate specific antigen. Int J Biol Macromol. 2019;126:1065-73. DOI: 10.1016/j.ijbiomac.2019.01.012

Díaz-Fernández A, Miranda-Castro R, de-los-Santos-Álvarez N, Rodríguez E, Lobo-Castañón M. Focusing aptamer selection on the glycan structure of prostate-specific antigen: Toward more specific detection of prostate cancer. Biosens Bioelectron. 2019;128:83-90. DOI: 10.1016/j.bios.2018.12.040

Stone N, Crawford E, editors. The prostate cancer dilemma. Switzerland: Springer; 2016. 230 p. DOI: 10.1007/978-3-319-21485-6

Access Hybritech PSA [Internet]. 2019 [cited 2019 Apr 11]. Available from:

Liu X, Wang D, Chu J, Xu Y, Wang W. Sandwich pair nanobodies, a potential tool for electrochemical immunosensing serum prostate-specific antigen with preferable specificity. J Pharm Biomed Anal. 2018;158:361-9. DOI: 10.1016/j.jpba.2018.06.021

Greene K, Albertsen P, Babaian R, Carter H, Gann P, Han M, et al. Prostate specific antigen best practice statement: 2009 update. J Urol. 2013;189(1S):25-86. DOI: 10.1016/j.juro.2012.11.014

Free PSA [I-125] IRMA KIT [Internet]. 2019 [cited 2019 Apr 11]. Available from:

Tosoian J, Loeb S. PSA and beyond: the past, present, and future of investigative biomarkers for prostate cancer. Sci World J. 2010;10:1919-31. DOI: 10.1100/tsw.2010.182

Adel Ahmed H, Azzazy H. Power-free chip enzyme immunoassay for detection of prostate specific antigen (PSA) in serum. Biosens Bioelectron. 2013;49:478-84. DOI: 10.1016/j.bios.2013.05.058

Shcherbina OV. The role of tumor markers in diagnosis of prostate gland cancer and the patient monitoring. Mezhdunarodnyiy Meditsinskiy Zhurnal. 2007;2:89-95.

Stenman UH, Paus E, Allard WJ, Andersson I,·Andrès C, Barnett TR, et al. Summary report of the TD-3 workshop: characterization of 83 antibodies against prostate-specific antigen. Tumor Biol. 1999;20(1):1-12. DOI: 10.1159/000056523

The Prostate Specific Antigen – α2-Macroglobulin complex: a significant form of total serum PSA [Internet]. 2019 [cited 2019 Apr 11]. Available from:

Klyuchko OM, Klyuchko ZF. Electronic information systems for monitoring of populations and migrations of insects. Biotechnologia Acta. 2018;11(5):5-25. DOI: 10.15407/biotech11.05.005

Klyuchko OM. Information computer technologies for using in biotechnology: electronic medical information systems. Biotechnologia Acta. 2018;11(3):5-26. DOI: 10.15407/biotech11.03.005

Hwang H, Choi E, Han S, Lee Y, Choi T, Kim M, et al. MESIA: Magnetic force-assisted electrochemical sandwich immunoassays for quantification of prostate-specific antigen in human serum. Anal Chim Acta. 2019;1061:92-100. DOI: 10.1016/j.aca.2019.02.018.

GOST Style Citations

Copyright (c) 2019 The Author(s)

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.