Russian Journal of BiotherapyRussian Journal of BiotherapyРоссийский биотерапевтический журнал1726-97841726-9792Publishing House ABV Press112410.17650/1726-9784-2018-17-4-45-51REVIEWSОБЗОРЫ ЛИТЕРАТУРЫBiomarkers of renal cell carcinomaБиомаркеры почечно-клеточного ракаAschubaS. A.АшубаС. А.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское шоссе, 24

Zanda82@mail.ruSolomkoE. S.СоломкоЭ. Ш.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское шоссе, 24

https://orcid.org/0000-0002-5694-3492KhochenkovD. A.ХоченковД. А.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское шоссе, 24

OsipovaA. A.ОсиповаА. А.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское шоссе, 24

StepanovaE. V.СтепановаЕ. В.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское шоссе, 24

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России11122018174455110012019100120192018https://bioterapevt.abvpress.ru/jour/article/view/1124

Renal cell carcinoma (RCC) ranks first in mortality among urogenital tumors and is the most common disease after prostate and bladder cancer. Early detection of RCC allows immediately undertaking appropriate treatment, which significantly increases the survival of patients. In the case of the asymptomatic RCC, timely diagnosis in the early stages is usually difficult. To date, the problem of searching for molecular markers of clear cell RCC, which allows to determine the stage, metastatic potential and prognosis of disease, or select a treatment regimen remains topical. Of particular interest are early-stage biomarkers of RCC and its metastatic potential, as well as markers that can be obtained by non-invasive or minimally invasive methods. This review presents modern methods for diagnosing RCC using biomarkers.

Почечно-клеточный рак (ПКР) занимает первое место по смертности среди урогенитальных опухолей и является самым распространенным заболеванием после рака предстательной железы и мочевого пузыря. Раннее выявление ПКР позволяет сразу проводить адекватное лечение и тем самым существенно увеличивать выживаемость пациентов. В случае бессимптомного протекания своевременная диагностика ПКР на ранних стадиях, как правило, затруднена. На сегодняшний день проблема поиска молекулярных маркеров светлоклеточного ПКР, позволяющих определить стадию, метастатический потенциал и прогноз заболевания, подобрать схему лечения остается актуальной. Особый интерес представляют биомаркеры раннего выявления ПКР и его метастатического потенциала, а также маркеры, которые могут быть получены неинвазивными или минимально инвазивными методами. В данном обзоре представлены современные способы диагностики ПКР с помощью биомаркеров.

renal cell carcinomabiomarkersangiogenesistargeted therapyпочечно-клеточный ракбиомаркерыангиогенезтаргетная терапия1. Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015;65(1):5–29. DOI: 10.3322/caac.21254.Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015;65(1):5–29. DOI: 10.3322/caac.21254.2. Злокачественные новообразования в России в 2015 году (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2015. 250 с. [Malignant neoplasms in Russia in 2015 (morbidity and mortality). Edited by A.D. Kaprin, V.V. Starinskiy, G.V. Petrova. Moscow: MNIOI im. P.A. Gertsena – filial FGBU “NMIRTS” Minzdrava Rossii, 2015. 250 p. (In Russ.)].Злокачественные новообразования в России в 2015 году (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2015. 250 с. [Malignant neoplasms in Russia in 2015 (morbidity and mortality). Edited by A.D. Kaprin, V.V. Starinskiy, G.V. Petrova. Moscow: MNIOI im. P.A. Gertsena – filial FGBU “NMIRTS” Minzdrava Rossii, 2015. 250 p. (In Russ.)].3. Опухоли почки. Морфологическая диагностика и генетика: Руководство. Под ред. Ю.Ю. Андреевой и Г.А. Франка. М., 2011, 66 с. [Tumors of the kidney. Morphological diagnosis and genetics: Guide. Under the editorship of Yu.Yu. Andreeva and G.A. Frank. M., 2011. 66 p. (In Russ.)].Опухоли почки. Морфологическая диагностика и генетика: Руководство. Под ред. Ю.Ю. Андреевой и Г.А. Франка. М., 2011, 66 с. [Tumors of the kidney. Morphological diagnosis and genetics: Guide. Under the editorship of Yu.Yu. Andreeva and G.A. Frank. M., 2011. 66 p. (In Russ.)].4. Kaelin W.G. Jr. The von Hippel-Lindau tumor suppressor gene and kidney cancer. Clin Cancer Res 2004; 10(18 Pt2):6290S – 5S. DOI: 10.1158/1078-0432.CCRsup-040025.Kaelin W.G. Jr. The von Hippel-Lindau tumor suppressor gene and kidney cancer. Clin Cancer Res 2004; 10(18 Pt2):6290S – 5S. DOI: 10.1158/1078-0432.CCRsup-040025.5. Goossens N., Nakagawa S., Sun X, Hoshida Y. Cancer biomarker discovery and validation. Transl Cancer Res 2015;4(3):256–9. DOI: 10.3978/j.issn.2218-676X. 2015.06.04.Goossens N., Nakagawa S., Sun X, Hoshida Y. Cancer biomarker discovery and validation. Transl Cancer Res 2015;4(3):256–9. DOI: 10.3978/j.issn.2218-676X. 2015.06.04.6. Снеговой А.В., Манзюк Л.В. Значение биомаркеров для определения тактики лечения и прогноза злокачественных опухолей. Практическая онкология 2011;12(4):166–70. [Snegovoi A.V., Manziuk L.V. The importance of biomarkers for determining treatment strategy and prognosis of malignant tumors. Practicheskaya Oncologiya = Practical Oncology 2011;12(4):166–70. (In Russ.)].Снеговой А.В., Манзюк Л.В. Значение биомаркеров для определения тактики лечения и прогноза злокачественных опухолей. Практическая онкология 2011;12(4):166–70. [Snegovoi A.V., Manziuk L.V. The importance of biomarkers for determining treatment strategy and prognosis of malignant tumors. Practicheskaya Oncologiya = Practical Oncology 2011;12(4):166–70. (In Russ.)].7. Cooper S.J., Tun H.W., Roper S.M. et al. Current status of biomarker discovery in human clear cell Renal cell carcinoma. J Mol Biomark Diagn 2012; S-2:1–10. DOI: 10.4172/2155-9929.S2-005.Cooper S.J., Tun H.W., Roper S.M. et al. Current status of biomarker discovery in human clear cell Renal cell carcinoma. J Mol Biomark Diagn 2012; S-2:1–10. DOI: 10.4172/2155-9929.S2-005.8. Li M., Rathmell W.K. Biomarkers for renal cell carcinoma. In the book:Kidney Cancer. Principles and Practice. Eds. Primo N. Lara Jr., Eric Jonasch. New York, 2012. Pp. 47–65.Li M., Rathmell W.K. Biomarkers for renal cell carcinoma. In the book:Kidney Cancer. Principles and Practice. Eds. Primo N. Lara Jr., Eric Jonasch. New York, 2012. Pp. 47–65.9. Yao M., Yoshida M., Kishida T. et al. VHL tumor suppressor gene alterations associated with good prognosis in sporadic clear-cell renal carcinoma. J Natl Cancer Inst 2002;94(20):1569–75. PMID: 12381710. DOI:10.1093/jnci/94.20.1569.Yao M., Yoshida M., Kishida T. et al. VHL tumor suppressor gene alterations associated with good prognosis in sporadic clear-cell renal carcinoma. J Natl Cancer Inst 2002;94(20):1569–75. PMID: 12381710. DOI:10.1093/jnci/94.20.1569.10. Schraml P., Struckmann K., Hatz F. et al. VHL mutations and their correlation with tumour cell proliferation, microvessel density, and patient prognosis in clear cell renal cell carcinoma. J Pathol 2002;196(2):186–93. PMID: 11793370. DOI: 10.1002/path.1034.Schraml P., Struckmann K., Hatz F. et al. VHL mutations and their correlation with tumour cell proliferation, microvessel density, and patient prognosis in clear cell renal cell carcinoma. J Pathol 2002;196(2):186–93. PMID: 11793370. DOI: 10.1002/path.1034.11. Bindra R.S., Vasselli J.R., Stearman R. et al. VHL-mediated Hypoxia Regulation of cyclin D1 in renal carcinoma cells. Cancer Res 2002;62(11):3014–9. PMID: 12036906.Bindra R.S., Vasselli J.R., Stearman R. et al. VHL-mediated Hypoxia Regulation of cyclin D1 in renal carcinoma cells. Cancer Res 2002;62(11):3014–9. PMID: 12036906.12. Choueiri T.K., Vaziri S.A., Jaeger E. et al. Von Hippel-Lindau gene status and response to vascular endothelial growth factor targeted therapy for metastatic clear cell renal cell carcinoma. J Urol 2008;180(3):860–5. DOI: 10.1016/j.juro.2008.05.015.Choueiri T.K., Vaziri S.A., Jaeger E. et al. Von Hippel-Lindau gene status and response to vascular endothelial growth factor targeted therapy for metastatic clear cell renal cell carcinoma. J Urol 2008;180(3):860–5. DOI: 10.1016/j.juro.2008.05.015.13. Rini B.I., Jaeger E., Weinberg V. et al. Clinical response to therapy targeted at vascular endothelial growth factor in metastatic renal cell carcinoma: impact of patient characteristics and Von Hippel-Lindau gene status. BJU Int 2006;98(4):756–62. PMID: 16827904. DOI: 10.1111/j.1464-410X.2006.06376.x.Rini B.I., Jaeger E., Weinberg V. et al. Clinical response to therapy targeted at vascular endothelial growth factor in metastatic renal cell carcinoma: impact of patient characteristics and Von Hippel-Lindau gene status. BJU Int 2006;98(4):756–62. PMID: 16827904. DOI: 10.1111/j.1464-410X.2006.06376.x.14. Choueiri T.K., Cheng S., Qu A.Q. et al. Carbonic anhydrase IX as a potential biomarker of efficacy in metastatic clearcell renal cell carcinoma patients receiving sorafenib or placebo: Analysis from the treatment approaches in renal cancer global evaluation trial(TARGET). Urol Oncol 2013;31(8):1788–93. PMID: 23141780. DOI: 10.1016/j.urolonc. 2012.07.004.Choueiri T.K., Cheng S., Qu A.Q. et al. Carbonic anhydrase IX as a potential biomarker of efficacy in metastatic clearcell renal cell carcinoma patients receiving sorafenib or placebo: Analysis from the treatment approaches in renal cancer global evaluation trial(TARGET). Urol Oncol 2013;31(8):1788–93. PMID: 23141780. DOI: 10.1016/j.urolonc. 2012.07.004.15. Peña C., Lathia C., Shan M. et al. Biomarkers predicting outcome in patients with advanced renal cell carcinoma: results from sorafenib phase III treatment approaches in renal cancer global evaluation trial. Clin Cancer Res 2010;16(19):4853–63. PMID: 20651059. DOI: 10.1158/1078-0432.CCR-09-3343.Peña C., Lathia C., Shan M. et al. Biomarkers predicting outcome in patients with advanced renal cell carcinoma: results from sorafenib phase III treatment approaches in renal cancer global evaluation trial. Clin Cancer Res 2010;16(19):4853–63. PMID: 20651059. DOI: 10.1158/1078-0432.CCR-09-3343.16. Тostain J., Li G., Gentil-Perret A., Gigante M. Carbonic anhydrase 9 in clear cell renal cell carcinoma: a marker for diagnosis, prognosis and treatment. Eur J Cancer 2010;46(18):3141–8. DOI: 10.1016/j.ejca.2010.07.020.Тostain J., Li G., Gentil-Perret A., Gigante M. Carbonic anhydrase 9 in clear cell renal cell carcinoma: a marker for diagnosis, prognosis and treatment. Eur J Cancer 2010;46(18):3141–8. DOI: 10.1016/j.ejca.2010.07.020.17. Zhao Z., Liao G., Li Y. et al. Prognostic value of carbonic anhydrase IX immunohistochemical expression in renal cell carcinoma: a meta-analysis of the literature. PLoS One 2014;9(11):e114096. PMID: 25426861. DOI: 10.1371/journal.pone.0114096.Zhao Z., Liao G., Li Y. et al. Prognostic value of carbonic anhydrase IX immunohistochemical expression in renal cell carcinoma: a meta-analysis of the literature. PLoS One 2014;9(11):e114096. PMID: 25426861. DOI: 10.1371/journal.pone.0114096.18. Горбань Н.А., Попов А.М., Карякин О.Б. Прогностическое значение экспрессии карбоангидразы 9 в сочетании с другими маркерами при светлоклеточном почечно-клеточном раке. Онкоурология 2016;12(3):40–4. [Gorban’ N. A., Popov A.M., Karyakin O.B. Prognostic value of the expression of carbonic anhydrase 9 in combination with other markers in patients with clear cell renal cell carcinoma. Onkourologiya = Cancer Urology 2016; 12(3):40–4 (In Russ.)]. DOI: 10.17650/1726-9776-2016-12-3-40-44.Горбань Н.А., Попов А.М., Карякин О.Б. Прогностическое значение экспрессии карбоангидразы 9 в сочетании с другими маркерами при светлоклеточном почечно-клеточном раке. Онкоурология 2016;12(3):40–4. [Gorban’ N. A., Popov A.M., Karyakin O.B. Prognostic value of the expression of carbonic anhydrase 9 in combination with other markers in patients with clear cell renal cell carcinoma. Onkourologiya = Cancer Urology 2016; 12(3):40–4 (In Russ.)]. DOI: 10.17650/1726-9776-2016-12-3-40-44.19. Dornbusch J., Zacharis A., Meinhardt M. et al. Analyses of potential predictive markers and survival data for a response to sunitinib in patients with metastatic renal cell carcinoma. PLoS One 2013;8(9):e76386. PMID: 24086736. DOI: 10.1371/journal.pone. 0076386.Dornbusch J., Zacharis A., Meinhardt M. et al. Analyses of potential predictive markers and survival data for a response to sunitinib in patients with metastatic renal cell carcinoma. PLoS One 2013;8(9):e76386. PMID: 24086736. DOI: 10.1371/journal.pone. 0076386.20. Gigante M., Li G., Ferlay C. et al. Prognostic value of serum CA9 in patients with metastatic clear cell renal cell carcinoma under targeted therapy. Anticancer Res 2012;32(12):5447–51. PMID: 23225450.Gigante M., Li G., Ferlay C. et al. Prognostic value of serum CA9 in patients with metastatic clear cell renal cell carcinoma under targeted therapy. Anticancer Res 2012;32(12):5447–51. PMID: 23225450.21. Choueiri T.K., Regan M.M., Rosenberg J.E. et al. Carbonic anhydrase IX and pathological features as predictors of outcome in patients with metastatic clear-cell renal cell carcinoma receiving vascular endothelial growth factortargeted therapy. BJU Int 2010;106(6):772–8. PMID: 20230385. DOI: 10.1111/j.1464-410X.2010.09218.x.Choueiri T.K., Regan M.M., Rosenberg J.E. et al. Carbonic anhydrase IX and pathological features as predictors of outcome in patients with metastatic clear-cell renal cell carcinoma receiving vascular endothelial growth factortargeted therapy. BJU Int 2010;106(6):772–8. PMID: 20230385. DOI: 10.1111/j.1464-410X.2010.09218.x.22. Stewart G.D., O’Mahony F.C., Laird A. et al. Carbonic anhydrase 9 expression increases with vascular endothelial growth factor – targeted therapy and is predictive of outcome in metastatic clear cell renal cancer. Eur Urol 2014;66(5):956–63. PMID: 24821582. DOI: 10.1016/j.eururo.2014.04.007.Stewart G.D., O’Mahony F.C., Laird A. et al. Carbonic anhydrase 9 expression increases with vascular endothelial growth factor – targeted therapy and is predictive of outcome in metastatic clear cell renal cancer. Eur Urol 2014;66(5):956–63. PMID: 24821582. DOI: 10.1016/j.eururo.2014.04.007.23. Kondo K., Kim W.Y., Lechpammer M. et al. Inhibition of HIF2alpha is sufficient to suppress pVHL-defective tumor growth. PLoS Biol 2003;1(3):E83. PMID: 14691554. DOI: 10.1371/journal.pbio.0000083.Kondo K., Kim W.Y., Lechpammer M. et al. Inhibition of HIF2alpha is sufficient to suppress pVHL-defective tumor growth. PLoS Biol 2003;1(3):E83. PMID: 14691554. DOI: 10.1371/journal.pbio.0000083.24. Klatte T., Seligson D.B., Riggs S.B. et al. Hypoxia-inducible factor 1 alpha in clear cell renal cell carcinoma. Clin Cancer Res 2007;13(24):7388–93. PMID: 18094421. DOI: 10.1158/1078-0432.CCR-07-0411.Klatte T., Seligson D.B., Riggs S.B. et al. Hypoxia-inducible factor 1 alpha in clear cell renal cell carcinoma. Clin Cancer Res 2007;13(24):7388–93. PMID: 18094421. DOI: 10.1158/1078-0432.CCR-07-0411.25. Lum J.J., Bui T., Gruber M. et al. The transcription factor HIF-1alpha plays a critical role in the growth factordependent regulation of both aerobic and anaerobic glycolysis. Genes Dev 2007;21(9):1037–49. PMID: 17437992. DOI: 10.1101/gad.1529107.Lum J.J., Bui T., Gruber M. et al. The transcription factor HIF-1alpha plays a critical role in the growth factordependent regulation of both aerobic and anaerobic glycolysis. Genes Dev 2007;21(9):1037–49. PMID: 17437992. DOI: 10.1101/gad.1529107.26. Covello K.L., Kehler J., Yu H. et al. HIF-2alpha regulates Oct-4: effects of hypoxia on stem cell function, embryonic development, and tumor growth. Genes Dev 2006;20(5):557–70. PMID: 16510872. DOI: 10.1101/gad.1399906.Covello K.L., Kehler J., Yu H. et al. HIF-2alpha regulates Oct-4: effects of hypoxia on stem cell function, embryonic development, and tumor growth. Genes Dev 2006;20(5):557–70. PMID: 16510872. DOI: 10.1101/gad.1399906.27. Gordan J.D., Thompson C.B., Simon M.C. HIF and c-Myc: sibling rivals for control of cancer cell metabolism and proliferation. Cancer Cell 2007;12(2):108–13. PMID: 17692803. DOI: 10.1016/j.ccr.2007.07.006.Gordan J.D., Thompson C.B., Simon M.C. HIF and c-Myc: sibling rivals for control of cancer cell metabolism and proliferation. Cancer Cell 2007;12(2):108–13. PMID: 17692803. DOI: 10.1016/j.ccr.2007.07.006.28. Kawata N., Nagane Y., Hirakata H. et al. Significant relationship of matrix metalloproteinase 9 with nuclear grade and prognostic impact of tissue inhibitor of metalloproteinase 2 for incidental clear cell renal cell carcinoma. Urology 2007;69(6):1049–53. PMID: 17572184. DOI: 10.1016/j.urology.2007.02.044.Kawata N., Nagane Y., Hirakata H. et al. Significant relationship of matrix metalloproteinase 9 with nuclear grade and prognostic impact of tissue inhibitor of metalloproteinase 2 for incidental clear cell renal cell carcinoma. Urology 2007;69(6):1049–53. PMID: 17572184. DOI: 10.1016/j.urology.2007.02.044.29. Minardi D., Lucarini G., Santoni M. et al. Survival in patients with clear cell renal cell carcinoma is predicted by HIF-1α expression. Anticancer Res 2015;35(1):433–8. PMID: 25550584.Minardi D., Lucarini G., Santoni M. et al. Survival in patients with clear cell renal cell carcinoma is predicted by HIF-1α expression. Anticancer Res 2015;35(1):433–8. PMID: 25550584.30. Patel P.H., Chadalavada R.S., Ishill N.M. et al. Hypoxia-inducible factor (HIF) 1a and 2a levels in cell lines and human tumor predicts response to sunitinib in renal cell carcinoma (RCC). J Clin Oncol 2008;26(15s):5008. PMID: 25550584. DOI:10.1200/jco.2008.26.15_suppl.5008.Patel P.H., Chadalavada R.S., Ishill N.M. et al. Hypoxia-inducible factor (HIF) 1a and 2a levels in cell lines and human tumor predicts response to sunitinib in renal cell carcinoma (RCC). J Clin Oncol 2008;26(15s):5008. PMID: 25550584. DOI:10.1200/jco.2008.26.15_suppl.5008.31. Harmon C.S., DePrimo S. E., Hutson T.E. et al. Circulating protein biomarkers of sunitinib and interferon-α efficacy in treatment-naive patients with metastatic renal cell carcinoma. Cancer Chemother Pharmacol 2014;73(1):151–61. PMID: 24220935. DOI: 10.1007/s00280-013-2333-4.Harmon C.S., DePrimo S. E., Hutson T.E. et al. Circulating protein biomarkers of sunitinib and interferon-α efficacy in treatment-naive patients with metastatic renal cell carcinoma. Cancer Chemother Pharmacol 2014;73(1):151–61. PMID: 24220935. DOI: 10.1007/s00280-013-2333-4.32. Maroto P., Rini B. Molecular biomarkers in advanced renal cell carcinoma. Clin Cancer Res. 2014;20(8):2060–71. PMID: 24526734. DOI: 10.1158/1078-0432.CCR-13-1351.Maroto P., Rini B. Molecular biomarkers in advanced renal cell carcinoma. Clin Cancer Res. 2014;20(8):2060–71. PMID: 24526734. DOI: 10.1158/1078-0432.CCR-13-1351.33. Frödin M., Mezheyeuski A., Corvigno S. et al. Perivascular PDGFR-β is an independent marker for prognosis in renal cell carcinoma. Br J Cancer 2017;116(2):195–201. PMID: 27931046. DOI:10.1038/bjc.2016.407.Frödin M., Mezheyeuski A., Corvigno S. et al. Perivascular PDGFR-β is an independent marker for prognosis in renal cell carcinoma. Br J Cancer 2017;116(2):195–201. PMID: 27931046. DOI:10.1038/bjc.2016.407.34. Garcia-Donas J., Leandro-García L.J., González Del Alba A. et al. Prospective study assessing hypoxia-related proteins as markers for the outcome of treatment with sunitinib in advanced clear-cell renal cell carcinoma. Ann Oncol 2013;24(9):2409–14. PMID: 23788753. DOI: 10.1093/annonc/mdt219.Garcia-Donas J., Leandro-García L.J., González Del Alba A. et al. Prospective study assessing hypoxia-related proteins as markers for the outcome of treatment with sunitinib in advanced clear-cell renal cell carcinoma. Ann Oncol 2013;24(9):2409–14. PMID: 23788753. DOI: 10.1093/annonc/mdt219.35. Cho N.H., Shim H.S., Rha S.Y. et al. Increased expression of matrix metalloproteinase 9 correlates with poor prognostic variables in renal cell carcinoma. Eur Urol 2003;44(5):560–6. PMID: 14572755. DOI:10.1016/s0302-2838(03)00362–2.Cho N.H., Shim H.S., Rha S.Y. et al. Increased expression of matrix metalloproteinase 9 correlates with poor prognostic variables in renal cell carcinoma. Eur Urol 2003;44(5):560–6. PMID: 14572755. DOI:10.1016/s0302-2838(03)00362–2.36. Гранов А.М., Якубович Е.И., Евтушенко В.И. Биспецифическая протеинкиназа dusp9 как новый диагностический маркер рака почки и перспективы ее пользования для генотерапии. Медицинский академический журнал 2012;12(3):7–14. [Granov A.M., Yakubovich E.I., Evtushenko V.I. Bispecific protein kinase phosphatase dusp9 as a new biomarker for clear cell renal cell carcinoma and prospects for its utilising for gene therapy. Medicinskij akademicheskij zhurnal = Med Academic J 2012;12(3):7–14. (In Russ.)].Гранов А.М., Якубович Е.И., Евтушенко В.И. Биспецифическая протеинкиназа dusp9 как новый диагностический маркер рака почки и перспективы ее пользования для генотерапии. Медицинский академический журнал 2012;12(3):7–14. [Granov A.M., Yakubovich E.I., Evtushenko V.I. Bispecific protein kinase phosphatase dusp9 as a new biomarker for clear cell renal cell carcinoma and prospects for its utilising for gene therapy. Medicinskij akademicheskij zhurnal = Med Academic J 2012;12(3):7–14. (In Russ.)].37. Golovastova M., Korolev D., Tsoy L. et al. Biomarkers of renal tumors: the current state and clinical perspectives. Curr Urol Rep 2017;18(1):3. PMID: 28110463. DOI: 10.1007/s11934-017-0655-1.Golovastova M., Korolev D., Tsoy L. et al. Biomarkers of renal tumors: the current state and clinical perspectives. Curr Urol Rep 2017;18(1):3. PMID: 28110463. DOI: 10.1007/s11934-017-0655-1.38. Stenman U.H. Tumor-associated trypsin inhibitor. Clin Chem 2002;48(8):1206–9. PMID: 12142374.Stenman U.H. Tumor-associated trypsin inhibitor. Clin Chem 2002;48(8):1206–9. PMID: 12142374.39. Xu Y., Li Q., Li X-Y. et al. Short-term anti-vascular endothelial growth factor treatment elicits vasculogenic mimicry formation of tumors to accelerate metastasis. J Exp Clin Cancer Res 2012;31(16):1–7. PMID: 22357313. DOI: 10.1186/1756-9966-31-16.Xu Y., Li Q., Li X-Y. et al. Short-term anti-vascular endothelial growth factor treatment elicits vasculogenic mimicry formation of tumors to accelerate metastasis. J Exp Clin Cancer Res 2012;31(16):1–7. PMID: 22357313. DOI: 10.1186/1756-9966-31-16.40. Huang X., Zuo J. Emerging roles of miR-210 and other non-coding RNAs in the hypoxic response. Acta Biochim Biophys Sin (Shanghai) 2014;46:220–32. PMID: 24395300. DOI: 10.1093/abbs/gmt141.Huang X., Zuo J. Emerging roles of miR-210 and other non-coding RNAs in the hypoxic response. Acta Biochim Biophys Sin (Shanghai) 2014;46:220–32. PMID: 24395300. DOI: 10.1093/abbs/gmt141.41. Redova M., Poprach A., Besse A. et al. MiR-210 expression in tumor tissue and in vitro effects of its silencing in renal cell carcinoma. Tumour Biol 2013;34(1):481–91. PMID: 23150176. DOI: 10.1007/s13277-012-0573-2.Redova M., Poprach A., Besse A. et al. MiR-210 expression in tumor tissue and in vitro effects of its silencing in renal cell carcinoma. Tumour Biol 2013;34(1):481–91. PMID: 23150176. DOI: 10.1007/s13277-012-0573-2.42. Zhao A., Li G., Peoc’h M., Gigante M. Serum miR-210 as a novel biomarker for molecular diagnosis of clear cell renal cell carcinoma. Exp Mol Pathol 2013;94(1):115–20. PMID: 23064048. DOI: 10.1016/j.yexmp.2012.10.005.Zhao A., Li G., Peoc’h M., Gigante M. Serum miR-210 as a novel biomarker for molecular diagnosis of clear cell renal cell carcinoma. Exp Mol Pathol 2013;94(1):115–20. PMID: 23064048. DOI: 10.1016/j.yexmp.2012.10.005.