Cancer UrologyCancer UrologyОнкоурология1726-97761996-1812Publishing House ABV Press130510.17650/1726-9776-2020-16-3-165-173REVIEWОБЗОРModern prostate cancer biomarkers. Prospects for EN2 in the prostate cancer diagnosisСовременные биомаркеры рака предстательной железы Перспективы EN2 в диагностике рака предстательной железыhttps://orcid.org/0000-0002-2851-2396TarabayevaA. S.ТарабаеваА. С.
Kazakhstan

94 Tole Bi St., Almaty 050000.

Тарабаева Анель Саидовна - профессор кафедры общей иммунологии, кандидат медицинских наук, доцент.050000 Алматы, Толе-би, 94.

tarabaeva60@mail.ruhttps://orcid.org/0000-0002-3841-938XZhubanturliyevaA. B.ЖубантурлиеваА. Б.
Kazakhstan

94 Tole Bi St., Almaty 050000.

Жубантурлиева Айнагуль Баубековна - доцент кафедры общей иммунологии.050000 Алматы, Толе-би, 94.

azhuban@mail.ruhttps://orcid.org/0000-0002-8290-5318OkhasI. M.ОхасИ. М.
Kazakhstan

94 Tole Bi St., Almaty 050000.

Охас Инкар Мырзахановна - ассистент кафедры общей иммунологии, магистр.050000 Алматы, Толе-би, 94.

ingkarokhas@gmail.comAsfendiyarov Kazakh National Medical UniversityКазахский Национальный медицинский университет им. С.Д. Асфендиярова300920201631651731405202024072020https://oncourology.abvpress.ru/oncur/article/view/1305

Prostate cancer is one of the most common forms of malignant neoplasms in men. In this regard, it is relevant to search for diagnostic markers that allow the creation of inexpensive, effective tests for early diagnosis of the disease, predicting the risk of relapse and assessing the effectiveness of the therapy. Existing invasive methods for diagnosing prostate cancer present some difficulties for patients. This article discusses the diagnostic capabilities of tissue biomarkers of prostate cancer obtained by non-invasive methods.

Рак предстательной железы является одной из наиболее распространенных форм злокачественных новообразований у мужчин. В связи с этим актуальным является поиск диагностических маркеров, позволяющих создание недорогих, эффективных тестов для ранней диагностики заболевания, предикции риска развития рецидивов и оценки эффективности проводимой терапии. Существующие инвазивные методы диагностики рака предстательной железы представляют некоторые затруднения для пациентов. В настоящей статье рассматриваются диагностические возможности тканевых биомаркеров рака предстательной железы, получаемые неинвазивными способами.

prostate cancerbiomarkerEN2 proteindiagnosticsрак предстательной железыбиомаркербелок EN2диагностикаhttps://www.wcrf.org/dietandcancer/cancer-trends/prostate-cancer-statistics.Ishkinin E.I., Nurgaliev N.S., Zhylkaidarova A.Zh. et al. Molecular genetic methods for the diagnosis of aggressive forms prostate cancer. Meditsina (Almaty) = Medicine (Almaty) 2018;9(195):37-40. (In Russ.).Ишкинин Е.И., Нургалиев Н.С., Жыл-кайдарова А.Ж. и др. Молекулярно-генетические способы диагностики агрессивных форм рака предстательной железы. Медицина (Алматы) 2018;9(195):37-40. DOI: 10.31082/1728-452X-2018-195-9-37-40.Strygina E.A., Medvedev V.L., Kurzanov A.N. Diagnostic and prognostic markers in prostate cancer. Sovremennyye problemy nauki i obrazovaniya = Modern Problems of Science and Education 2016;2. Available at: http://www.science-education.ru/ru/article/view?id=24439. (In Russ.).Стрыгина Е.А., Медведев В.Л., Курза-нов А.Н. Диагностические и прогностические маркеры рака предстательной железы. Современные проблемы науки и образования 2016;2. Доступно по: http://www.science-education.ru/ru/article/view?id=24439.Loeb S., Catalona W.J. The Prostate Health Index: a new test for the detection of prostate cancer. Ther Adv Urol 2014;6(2):74-7. DOI: 10.1177/1756287213513488.Guazzoni G., Nava L., Lazzeri M. et al. Prostate-specific antigen (PSA) isoform p2PSA significantly improves the prediction of prostate cancer at initial extended prostate biopsies in patients with total PSA between 2.0 and 10 ng/ml: results of a prospective study in a clinical setting. Eur Urol 2011;60: 214-22. DOI: 10.1016/j.eururo.2011.03.052.Scattoni V., Lazzeri M., Lughezzani G. et al. Head-to-head comparison of prostate health index and urinary PCA3 for predicting cancer at initial or repeat biopsy. J Urol 2013;190(2):496-501. DOI: 10.1016/j.juro.2013.02.3184.Loeb S., Sanda M.G., Broyles D.L. et al. The prostate health index selectively identifies clinically significant prostate cancer. J Urol 2015;193(4):1163-9. DOI: 10.1016/j.juro.2014.10.121.Boegemann M., Stephan C., Cammann H. et al. The percentage of prostate-specific antigen (PSA) isoform [-2]proPSA and the Prostate Health Index improve the diagnostic accuracy for clinically relevant prostate cancer at initial and repeat biopsy compared with total PSA and percentage free PSA in men aged <65 years. BJU Int 2016;117(1):72-9. DOI: 10.1111/bju.13139.Sokoll L.J., Sanda M.G., Feng Z. et al. A prospective, multicenter, National Cancer Institute Early Detection Research Network study of [—2]proPSA: improving prostate cancer detection and correlating with cancer aggressiveness. Cancer Epidemiol Biomarkers Prev 2010;19(5):1193-200. DOI: 10.1158/1055-9965.EPI-10-0007.Truong M., Yang B., Jarrard D.F. Toward the detection of prostate cancer in urine: a critical analysis. J Urol 2013;189:422-9. DOI: 10.1016/j.juro.2012.04.143.de la Taille A., Irani J., Graefen M. et al. Clinical evaluation of the PCA3 assay in guiding initial biopsy decisions. J Urol 2011;185:2119-25. DOI: 10.1016/j.juro.2011.01.075.Wei J.T., Feng Z., Partin A.W. et al. Can urinary PCA3 supplement PSA in the early detection of prostate cancer? J Clin Oncol 2014;32:4066-7. DOI: 10.1200/JCO.2013.52.8505.Auprich M., Augustin H., Budaus L. et al. A comparative performance analysis of total prostate-specific antigen, percentage free prostate-specific antigen, prostatespecific antigen velocity and urinary prostate cancer gene 3 in the first, second and third repeat prostate biopsy. BJU Int 2012;109: 1627-35. DOI: 10.1111/j.1464-410X.2011.10584.x.Toropovskiy A.N., Nikitin A.G., Pavlova O.N. et al. Perspectives of improvement of the diagnosis of prostate cancer based on analysis of PCA3 gene expression. Urologiya = Urology 2019;(2):82-6. (In Russ.).Тороповский А.Н., Никитин А.Г., Павлова О.Н. и др. Перспективы совершенствования диагностики рака предстательной железы на основе анализа экспрессии гена РСА3. Урология 2019;(2):82-6. DOI: 10.18565/urology.2019.2.82-86.Kar A., Gutierrez-Hartmann A. Molecular mechanisms of ETS transcription factor-mediated tumorigenesis. Critical Rev Biochem Mol Biol 2013;48(6):522-43. DOI: 10.3109/10409238.2013.838202.Sanguedolce F., Cormio A., Brunelly M. et al. Urine TMPRSS2:ERG fusion transcript as a biomarker for prostate cancer: literature review. Clin Genitourinary Cancer 2016;14(2):117-21. DOI: 10.1016/j.clgc.2015.12.001.Fallahabadi Z.R., Daloii M., Mahdian R. et al. Frequency of PTEN alterations, TMPRSS2-ERG fusion and their association in prostate cancer. Gene 2016;575(2):755-60. DOI: 10.1016/j.gene.2015.09.068.Noh B.J., Sung J.Y., Kim Y.W. et al. Prognostic value of ERG, PTEN, CRISP3 and SPINK1 in predicting biochemical recurrence in prostate cancer. Oncol Lett 2016;11(6):3621-30. DOI: 10.3892/ol.2016.4459.Merdan S., Tomlins S.A., Barnett C. et al. Assessment of long term outcomes associated with urinary prostate cancer antigen 3 and TMPRSS2:ERG gene fusion at repeat biopsy. Cancer 2015;121(22):4071-9. DOI: 10.1002/cncr.29611.Apolikhin O.I., Sivkov A.V., Efremov G.D. et al. The first Russian experience of using PCA3 and TMPRSS2-ERG for prostate cancer diagnosis. Eksperimental'naya i klinicheskaya urologiya = Experimental and Clinical Urology 2015;(2):30-6. (In Russ.).Аполихин О.И., Сивков А.В., Ефремов Г.Д. и др. PCA3 и TMPRSS2-ERG в диагностике рака предстательной железы: первый опыт применения комбинации маркеров в России. Экспериментальная и клиническая урология 2015;(2):30-6.Maslyakov V.V., Grebnev D.Yu., Prokhorenko I.O. Changes in the levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients with basal cell skin carcinoma in response to surgical treatment. Vestnik meditsinskogo instituta “Reaviz” = Bulletin of Medical Institute “Reaviz” 2018;(4):101-5. (In Russ.).Масляков В.В., Гребнев Д.Ю., Прохоренко И.О. Динамика металлопротеиназ и их тканевых ингибиторов при базальноклеточном раке кожи в процессе оперативного лечения. Вестник медицинского института «Реавиз» 2018;(4):101-5.Kushlinskii N.E., Gershtein E.S., Ivannikov A.A. et al. Clinical significance of matrix metalloproteinases in blood plasma of patients with gastric cancer. Byulleten' eksperimental'noy biologii i meditsiny = Bulletin of Experimental Biology and Medicine 2018;(9):347-51. (In Russ.).Кушлинский Н.Е., Герштейн Е.С., Иванников А.А. и др. Клиническое значение матриксных металлопротеиназ в плазме крови больных раком желудка. Бюллетень экспериментальной биологии и медицины 2018;(9):347-51. DOI: 10.1007/s10517-019-04353-y.Kushlinskii N.E., Gershtein E.S., Alferov A.A. et al. Prognostic role of matrix metalloproteinases 2, 7, 8, 9 and their type 1 tissue inhibitor in blood serum of patients with kidney cancer. Byulleten' eksperimental'noy biologii i meditsiny = Bulletin of Experimental Biology and Medicine 2020;168:673-6. (In Russ.).Кушлинский Н.Е., Герштейн Е.С., Алферов А.А. и др. Прогностическое значение матриксных металлопротеиназ 2, 7, 8, 9 и их тканевого ингибитора 1-го типа в сыворотке крови больных раком почки. Бюллетень экспериментальной биологии и медицины 2020;168:673-6. DOI: 10.1007/s10517-020-04778-w.Aksenenko M.B., Ruksha T.G. Expression of nuclear matrix metalloproteinase 2 in patients with cutaneous melanoma depending on the availability of mutations in the PPP6C genes. Rossiyskiy zhurnal kozhnykh i venericheskikh bolezney = Russian Journal of Skin and Venereal Diseases 2018;(1):4-9. (In Russ.).Аксененко М.Б., Рукша Т.Г. Внутриклеточная экспрессия матриксной металлопротеиназы 2 и ее зависимость от РРР6С-мутационного статуса при меланоме кожи. Российский журнал кожных и венерических болезней 2018;(1):4-9. DOI: 10.18821/1560-95882018-21-1-4-9.Geng X., Chen C., Huang Y. et al. The prognostic value and potential mechanism of matrix metalloproteinases among prostate cancer. Int J Med Sci 2020;17(11):1550-60. DOI: 10.7150/ijms.46780.Tikhonova M.V., Karachunskiy A.I., Pospelov V.I. et al. Prospects of exosomes use of tumor cells in the diagnosis, monitoring and therapy of malignant diseases. Rossiyskiy zhurnal detskoy gematologii i onkologi = Russian Journal of Pediatric Hematology and Oncology 2017;(2):40-5. (In Russ.).Тихонова М.В., Карачунский А.И., Поспелов В.И. и др. Перспективы использования экзосом опухолевых клеток в диагностике, мониторинге и терапии злокачественных заболеваний. Российский журнал детской гематологии и онкологии 2017;(2):40-5. DOI: 10.17650/2311-1267-2017-4-2-40-45.Malek A.V., Samsonov R.B., Chiesi A. Development of cancer diagnostics and monitoring methods based on analysis of tumor-derived exosomes. Rossiyskiy bioterapevticheskiy zhurnal = Russian Journal of Biotherapy 2015;4(14):9-18. (In Russ.).Малек А.В., Самсонов Р.Б., Кьези А. Перспективы разработки методов диагностики и мониторинга онкологических заболеваний на основе анализа экзосом, секретируемых опухолевыми клетками. Российский биотерапевти-ческий журнал 2015;4(14):9-18.McKiernan J., Donovan M.J., O'Neill V. et al. A novel urine exosome gene expression assay to predict high-grade prostate cancer at initial biopsy. JAMA Oncology 2016;2:882-9. DOI: 10.1001/jamaoncol.2016.0097.Donovan M.J., Noerholm M., Bentink S. et al. A molecular signature of PCA3 and ERG exosomal RNA from non-DRE urine is predictive of initial prostate biopsy result. Prostate Cancer Prostatic Dis 2015; 18:370-5. DOI: 10.1038/pcan.2015.40.Martin N.L., Saba-El-Leil M.K., Sadekova S. et al. EN2 is a candidate oncogene in human breast cancer. Oncogene 2005;24(46):6890-901. DOI: 10.1038/sj.onc.1208840.Michael A., Riley C., Boakee S. et al. EN2: a candidate antigen for the development of targeted therapies in ovarian cancer. J Clin Oncol 2011;29. DOI: 10.1200/jco.2011.29.15_suppl.e15528.McGrath S.E., Annels N., Madhuri T.K. et al. Engrailed-2 (EN2) - a novel biomarker in epithelial ovarian cancer. BMC Cancer 2018;18:943. DOI: 10.1186/s12885-018-4816-5.Morgan R., Bryan R.T., Javed S. et al. Expression of Engrailed-2 (EN2) protein in bladder cancer and its potential utility as a urinary diagnostic biomarker. Eur J Cancer 2013;49(9):2214-22. DOI: 10.1016/j.ejca.2013.01.019.Bose S.K., Bullard R.S., Donald C.D. Oncogenic role of engrailed-2 (EN-2) in prostate cancer cell growth and survival. Transl Oncogenomics 2008;3:37-43. DOI: 10.4137/TOG.S369.Rauch T., Wang Z., Zhang X. et al. Homeobox gene methylation in lung cancer studied by genome-wide analysis with a microarray-based methylated CpG island recovery assay. Proc Natl Acad Sci USA 2007;104(13):5527-32. DOI: 10.1073/pnas.0701059104.Karpinski P., Ramsey D., Grzebieniak Z. et al. The CpG island methylator phenotype correlates with long-range epigenetic silencing in colorectal cancer. Mol Cancer Res 2008;6(4):585-91. DOI: 10.1158/1541-7786.MCR-07-2158.Mayor R., Casadome L., Azuara D. et al. Long-range epigenetic silencing at 2q14.2 affects most human colorectal cancers and may have application as a non-invasive biomarker of disease. Br J Cancer 2009;100(10):1534-9. DOI: 10.1038/sj.bjc.6605045.Wu X., Rauch T.A., Zhong X. et al. CpG island hypermethylation in human astrocytomas. Cancer Res 2010;70(7):2718-27. DOI: 10.1158/0008-5472.CAN-09-3631.Devaney J., Stirzaker C., Qu W. et al. Epigenetic deregulation across chromosome 2q14.2 differentiates normal from prostate cancer and provides a regional panel of novel DNA methylation cancer biomarkers. Cancer Epidemiol Biomarkers Prev 2011;20(1):148-59. DOI: 10.1158/1055-9965.EPI-10-0719.Bennett L.B., Schnabel J.L., Kelchen J.M. et al. DNA hypermethylation accompanied by transcriptional repression in follicular lymphoma. Genes Chromosomes Cancer 2009;48(9):828-41. DOI: 10.1002/gcc.20687.Cunningham D., You Z. In vitro and in vivo model systems used in prostate cancer research. J Biol Methods 2015;2(1):e17. DOI: 10.14440/jbm.2015.63.Baron V.T., Pio R., Jia Z. et al. Early Growth Response 3 regulates genes of inflammation and directly activates IL6 and IL8 expression in prostate cancer. Br J Cancer 2015;112:755-64. DOI: 10.1038/bjc.2014.622.Pio R., Jia Z., Baron V.T. et al. Early growth response 3 (Egr3) is highly overexpressed in non-relapsing prostate cancer but not in relapsing prostate cancer. PLoS One 2013;8:e54096. DOI: 10.1371/journal.pone.0054096.Gomez-Gomez Е., Jimenez-Vacas J.M., Pedraza-Arevalo S. et al. Oncogenic role of secreted Engrailed Homeobox 2 (EN2) in prostate cancer. J Clin Med 2019;8(9):1400. DOI: 10.3390/jcm8091400.Cantile M., Franco R., Schiavo G. et al. The HOX genes network in uro-genital cancers: mechanisms and potential therapeutic implications. Curr Med Chem 2011;18:4872-84. DOI: 10.2174/092986711797535182.Killick E., Morgan R., Launchbury F. et al. Role of Engrailed-2 (EN2) as a prostate cancer detection biomarker in genetically high risk men. Scic Rep 2013;3:1-5. DOI: 10.1038/srep02059.Pandha H., Sorensen K.D., Orntoft T.F. et al. Urinary engrailed-2 (EN2) levels predict tumour volume in men undergoing radical prostatectomy for prostate cancer. BJU Int 2012;110:E287-92. DOI: 10.1111/j.1464-410X.2012.11208.x.Pandha H., Javed S., Sooriakumaran P. et al. Correlation of urinary engrailed-2 levels to tumour volume and pathological stage in men undergoing radical prostatectomy. J Cancer Ther 2013;24:726-33. DOI: 10.4236/jct.2013.43089.Do Carmo Silva J., Vesely S., Novak V. et al. Is Engrailed-2 (EN2) a truly promising biomarker in prostate cancer detection? Biomarkers 2020;25(1):34-9. DOI: 10.1080/1354750X.2019.1690047.Rosa M.I.D., Dondossola E.R., Alexandre M.C.M. et al. Urinary EN-2 to predict prostate cancer: systematic review and meta-analysis. Rev Assoc Med Bras (1992) 2017;63(7):656-61. DOI: 10.1590/1806-9282.63.07.656.Marszall M.P., Sroka W., Adamowski M. et al. Engrailed-2 protein as a potential urinary prostate cancer biomarker: a comparison study before and after digital rectal examination. Eur J Cancer Prev 2015;24:51-6. DOI: 10.1097/CEJ.0000000000000046.Morgan R., Boxall A., Bhatt A. et al. Engrailed-2 (EN2): a tumor specific urinary biomarker for the early diagnosis of prostate cancer. Clin Cancer Res 2011;17:1090-8. DOI: 10.1158/1078-0432.CCR-10-2410.Thomas C.E., Sexton W., Benson K. et al. Urine collection and processing for protein biomarker discovery and quantification. Cancer Epidemiol Biomarkers Prev 2010;19:953-9. DOI: 10.1158/1055-9965.EPI-10-0069.Xu L., Wen Y., Pandit S. et al. Graphenebased biosensors for the detection of prostate cancer protein biomarkers: a review. BMC Chem 2019;13(1):112. DOI: 10.1186/s13065-019-0611-x.Lee S., Jo H., Her J. et al. Ultrasensitive electrochemical detection of engrailed-2 based on homeodomain-specific DNA probe recognition for the diagnosis of prostate cancer. Biosens Bioelectron 2015;66:32-8. DOI: 10.1016/j.bios.2014.11.003.