Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press14910.17650/2313-805X-2018-5-2-62-70RESEARCH ARTICLESЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИEXPRESSION OF CANCER-TESTIS GENES PRAME, NY-ESO1, GAGE1, MAGE A3, MAGE A6, MAGE A12, SSX1, SLLP1, PASD1 IN PATIENTS WITH MULTIPLE MYELOMA, THEIR INFLUENCE ON OVERALL SURVIVAL AND RELAPSE RATEЭКСПРЕССИЯ РАКОВО-ТЕСТИКУЛЯРНЫХ ГЕНОВ PRAME, NY-ESO1, GAGE1, MAGE A3, MAGE A6, MAGE A12, SSX1, SLLP1, PASD1 У БОЛЬНЫХ МНОЖЕСТВЕННОЙ МИЕЛОМОЙ, ИХ ВЛИЯНИЕ НА ПОКАЗАТЕЛИ ОБЩЕЙ ВЫЖИВАЕМОСТИ И СКОРОСТЬ ВОЗНИКНОВЕНИЯ РЕЦИДИВАhttps://orcid.org/0000-0001-8399-057XSolodovnikA. A.СолодовникА. А.
Russian Federation

24 Kashirskoe Shosse,  Moscow 115478

Алена Александровна Солодовник.

115478 Москва, Каширское шоссе, 24

alionka1363@rambler.ruhttps://orcid.org/0000-0002-0638-213XMkrtchyanH. S.МкртчянА. С.
Russian Federation

104 Profsoyuznaya St., Moscow 117485

17279 Москва, ул. Профсоюзная, 104

https://orcid.org/0000-0002-0762-5631MisyurinV. A.МисюринВ. А.
Russian Federation

24 Kashirskoe Shosse,  Moscow 115478

115478 Москва, Каширское шоссе, 24

https://orcid.org/0000-0002-8658-2819TikhonovaV. V.ТихоноваВ. В.
Russian Federation

24 Kashirskoe Shosse,  Moscow 115478

115478 Москва, Каширское шоссе, 24

https://orcid.org/0000-0002-6154-535XFinashutinaYu. P.ФинашутинаЮ. П.
Russian Federation

24 Kashirskoe Shosse,  Moscow 115478

115478 Москва, Каширское шоссе, 24

https://orcid.org/0000-0002-4735-977XKasatkinaN. N.КасаткинаН. Н.
Russian Federation

24 Kashirskoe Shosse,  Moscow 115478

115478 Москва, Каширское шоссе, 24

SolopovaO. N.СолоповаО. Н.
Russian Federation

24 Kashirskoe Shosse,  Moscow 115478

115478 Москва, Каширское шоссе, 24

VotyakovaO. M.ВотяковаО. М.
Russian Federation

24 Kashirskoe Shosse,  Moscow 115478

115478 Москва, Каширское шоссе, 24

https://orcid.org/0000-0002-4309-2473YakimovichO. Yu.ЯкимовичО. Ю.
Russian Federation

24 Kashirskoe Shosse,  Moscow 115478

115478 Москва, Каширское шоссе, 24

VolodinaO. M.ВолодинаО. М.
Russian Federation

24 Kashirskoe Shosse,  Moscow 115478

115478 Москва, Каширское шоссе, 24

KichiginaM. Yu.КичигинаМ. Ю.
Russian Federation

24 Kashirskoe Shosse,  Moscow 115478

115478 Москва, Каширское шоссе, 24

https://orcid.org/0000-0001-9615-6090MedvedovskayaE. G.МедведовскаяЕ. Г.
Russian Federation

24 Kashirskoe Shosse,  Moscow 115478

115478 Москва, Каширское шоссе, 24

https://orcid.org/0000-0002-1731-8336AntipovaA. S.АнтиповаА. С.
Russian Federation

24 Kashirskoe Shosse,  Moscow 115478

115478 Москва, Каширское шоссе, 24

https://orcid.org/0000-0001-6674-8634ZavodnovaI. Z.ЗаводноваИ. З.
Russian Federation

24 Kashirskoe Shosse,  Moscow 115478

115478 Москва, Каширское шоссе, 24

SemenovaA. A.СеменоваА. А.
Russian Federation

24 Kashirskoe Shosse,  Moscow 115478

115478 Москва, Каширское шоссе, 24

ArakelyanG. R.АракелянГ. Р.
Russian Federation

24 Kashirskoe Shosse,  Moscow 115478

115478 Москва, Каширское шоссе, 24

RyabukhinaYu. E.РябухинаЮ. Е.
Russian Federation

24 Kashirskoe Shosse,  Moscow 115478

115478 Москва, Каширское шоссе, 24

https://orcid.org/0000-0003-3430-8540KolomeytsevO. A.КоломейцевО. А.
Russian Federation

24 Kashirskoe Shosse,  Moscow 115478

115478 Москва, Каширское шоссе, 24

https://orcid.org/0000-0003-3244-7774ShirinA. D.ШиринА. Д.
Russian Federation

24 Kashirskoe Shosse,  Moscow 115478

115478 Москва, Каширское шоссе, 24

https://orcid.org/0000-0002-3067-1601OsmanovE. A.ОсмановЕ. А.
Russian Federation

Build. 2, 8 Trubetskaya St., Moscow 119991 

119991 Москва, ул. Трубецкая, 8, стр. 2

https://orcid.org/0000-0003-1349-2879MisyurinA. V.МисюринА. В.
Russian Federation

24 Kashirskoe Shosse,  Moscow 115478; 104 Profsoyuznaya St., Moscow 117485 

115478 Москва, Каширское шоссе, 24; 17279 Москва, ул. Профсоюзная, 104

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н. Н. Блохина» Минздрава РоссииGeneTechnologyООО ГеноТехнологияI.M. Sechenov First Moscow State Medical University, Ministry of Health of RussiaФГАОУ ВО Первый Московский государственный медицинский университет им. И.М. Сеченова Минздрава России150520185262701807201818072018Copyright ©; 2018, Solodovnik A.A., Mkrtchyan H.S., Misyurin V.A., Tikhonova V.V., Finashutina Y.P., Kasatkina N.N., Solopova O.N., Votyakova O.M., Yakimovich O.Y., Volodina O.M., Kichigina M.Y., Medvedovskaya E.G., Antipova A.S., Zavodnova I.Z., Semenova A.A., Arakelyan G.R., Ryabukhina Y.E., Kolomeytsev O.A., Shirin A.D., Osmanov E.A., Misyurin A.V.Copyright ©; 2018, Солодовник А.А., Мкртчян А.С., Мисюрин В.А., Тихонова В.В., Финашутина Ю.П., Касаткина Н.Н., Солопова О.Н., Вотякова О.М., Якимович О.Ю., Володина О.М., Кичигина М.Ю., Медведовская Е.Г., Антипова А.С., Заводнова И.З., Семенова А.А., Аракелян Г.Р., Рябухина Ю.Е., Коломейцев О.А., Ширин А.Д., Османов Е.А., Мисюрин А.В.2018Solodovnik A.A., Mkrtchyan H.S., Misyurin V.A., Tikhonova V.V., Finashutina Y.P., Kasatkina N.N., Solopova O.N., Votyakova O.M., Yakimovich O.Y., Volodina O.M., Kichigina M.Y., Medvedovskaya E.G., Antipova A.S., Zavodnova I.Z., Semenova A.A., Arakelyan G.R., Ryabukhina Y.E., Kolomeytsev O.A., Shirin A.D., Osmanov E.A., Misyurin A.V.Солодовник А.А., Мкртчян А.С., Мисюрин В.А., Тихонова В.В., Финашутина Ю.П., Касаткина Н.Н., Солопова О.Н., Вотякова О.М., Якимович О.Ю., Володина О.М., Кичигина М.Ю., Медведовская Е.Г., Антипова А.С., Заводнова И.З., Семенова А.А., Аракелян Г.Р., Рябухина Ю.Е., Коломейцев О.А., Ширин А.Д., Османов Е.А., Мисюрин А.В.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/149

Objective: to study the prognostic significance of the expression of cancer-testis (CT) genes PRAME, NY-ESO1, GAGE1, MAGE A3, MAGE A6, MAGE A12, SSX1, SLLP1, PASD1 in patients with multiple myeloma (MM) and their influence on overall survival and relapse rate. To determine their effect on suсh clinical parameters as levels of lactate dehydrogenase, leucocytes, hemoglobin, calcium, albumen, creatinine, beta-2-microglobulin.

Materials and methods. Real-time polymerase chain reaction was performed on complementary DNA obtained from bone marrow of 77 patients with MM. The statistical analysis was performed using the Statistica 10.0 software package. To estimate prognostic values of the CT gene expression data were analyzed by the Kaplan – Meier method.

Results. The study was conducted to determine the level of expression of CT genes PRAME, NY-ESO1, GAGE1, MAGE A3, MAGE A6, MAGE A12, SSX1, SLLP1, PASD1 in a group of patients with MM. The group included primary and receiving cancer treatment in MM patients. According to the log-rank criterion expression of any of the CT genes PRAME, NY-ESO1, GAGE1, MAGE A3, MAGE A6, MAGE A12, SSX1, SLLP1, PASD1 exerts a significant influence on overall survival and progression-free survival/relapse. It was also determined that providing expression of some CT genes, the levels of creatinine, calcium, beta-2-microglobulin were much higher to compare with patients without expression.

cancer-testis genesmultiple myelomaoverall survivalprogression-free survivalраково-тестикулярный генмножественная миеломаобщая выживаемостьбезрецидивная выживаемостьGeneTechnologyООО «ГеноТехнология»Scanlan M. J., Simpson A. J., Old L. J. The cancer/testis genes: review, standardization, and commentary. Cancer Immun 2004;4:1. PMID: 14738373.Chen Y. T., Scanlan M. J., Sahin U. et al. A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc Natl Acad Sci USA 1997;94(5):1914–8. PMID: 9050879.Chen Y. T., Scanlan M. J., Sahin U. et al. A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc Natl Acad Sci USA 1997;94(5):1914–8. PMID: 9050879.Scanlan M. J., Gure A. O., Jungbluth A. A. et al. Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunol Rev 2002;188:22–32. PMID: 12445278.Scanlan M. J., Gure A. O., Jungbluth A. A. et al. Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunol Rev 2002;188:22–32. PMID: 12445278.Simpson A. J., Caballero O. L., Jungbluth A. et al. Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer 2005;5(8):615–25. DOI: 10.1038/nrc1669. PMID: 16034368.Mirandola L., Cannon M. J., Cobos E. et al. Cancer testis antigens: novel biomarkers and targetable proteins for ovarian cancer. Int Rev Immunol 2011;30(2–3):127–37. DOI: 10.3109/08830185.2011.572504. PMID: 21557639.Mirandola L., Cannon M. J., Cobos E. et al. Cancer testis antigens: novel biomarkers and targetable proteins for ovarian cancer. Int Rev Immunol 2011;30(2–3):127–37. DOI: 10.3109/08830185.2011.572504. PMID: 21557639.Misyurin V. A. X-chromosomal cancer-testis genes. Rossiyskiy bioterapevticheskiy zhurnal = Russian Biotherapeutic Journal 2014;13(2):3–9. (In Russ.)Мисюрин В. А. Х-хромосомные раково-тестикулярные гены. Российский биотерапевтический журнал 2014;13(2):3–9.Fratta E., Coral S., Covre A. et al. The biology of cancer testis antigens: putative function, regulation and therapeutic potential. Mol Oncol 2011;5(2):164–82. DOI: 10.1016/j.molonc.2011.02.001. PMID: 21376678.Song M. H., Ha J. C., Lee S. M. et al. Identification of BCP-20 (FBXO39) as a cancer/testis antigen from colon cancer patients by SEREX. Biochem Biophys Res Commun 2011;408(2):195–201. DOI: 10.1016/j.bbrc.2011.02.077. PMID: 21338577.Song M. H., Ha J. C., Lee S. M. et al. Identification of BCP-20 (FBXO39) as a cancer/testis antigen from colon cancer patients by SEREX. Biochem Biophys Res Commun 2011;408(2):195–201. DOI: 10.1016/j.bbrc.2011.02.077. PMID: 21338577.Chen Y. T., Ross D. S., Chiu R. et al. Multiple cancer/testis antigens are preferentially expressed in hormonereceptor negative and high-grade brease cancers. PLoS One 2011;6(3):17876. DOI: 10.1371/journal.pone.0017876. PMID: 21437249.Chen Y. T., Ross D. S., Chiu R. et al. Multiple cancer/testis antigens are preferentially expressed in hormonereceptor negative and high-grade brease cancers. PLoS One 2011;6(3):17876. DOI: 10.1371/journal.pone.0017876. PMID: 21437249.Boss D. S., Glen H., Beijnen J. H. et al. Serum β-HCG and CA-125 as tumor markers in a patient with osteosarcoma: case report. Tumori 2011;97(12):109–14. PMID: 21528673.Boss D. S., Glen H., Beijnen J. H. et al. Serum β-HCG and CA-125 as tumor markers in a patient with osteosarcoma: case report. Tumori 2011;97(12):109–14. PMID: 21528673.Silina K., Zayakin P., Kalnina Z. et al. Sperm-associated antigens as targets for cancer immunotheraphy: expression pattern and humoral immune response in cancer patients. J Immunother 2011;34(1):28–44. DOI: 10.1097/CJI.0b013e3181fb64fa. PMID: 21150711.Silina K., Zayakin P., Kalnina Z. et al. Sperm-associated antigens as targets for cancer immunotheraphy: expression pattern and humoral immune response in cancer patients. J Immunother 2011;34(1):28–44. DOI: 10.1097/CJI.0b013e3181fb64fa. PMID: 21150711.Maruyama M., Yoshitake Н.Т.Н., Takamori K., Araki Y. Molecular expression of Ly6k, a putative glycosylphosphatidyl- inositol-anchored membrane protein on the mouse testicular germ cells. Biochem Biophys Res Commun 2010;402(1):75–81. DOI: 10.1016/j.bbrc.2010.09.117. PMID: 20920470.Maruyama M., Yoshitake Н.Т.Н., Takamori K., Araki Y. Molecular expression of Ly6k, a putative glycosylphosphatidyl- inositol-anchored membrane protein on the mouse testicular germ cells. Biochem Biophys Res Commun 2010;402(1):75–81. DOI: 10.1016/j.bbrc.2010.09.117. PMID: 20920470.Matsuda R., Enokida H., Chiyomaru T. et al. LY6K is a novel molecular target in blader cancer on basis of integrate genome-wide profiling. Br J Cancer 2011;104(2):376–86. DOI: 10.1038/sj.bjc.6605990. PMID: 21063397.Matsuda R., Enokida H., Chiyomaru T. et al. LY6K is a novel molecular target in blader cancer on basis of integrate genome-wide profiling. Br J Cancer 2011;104(2):376–86. DOI: 10.1038/sj.bjc.6605990. PMID: 21063397.Li F. Q., Liu Q., Han Y. L. et al. Sperm protein 17 is highly expressed in endometrial and cervical cancers. BMC Cancer 2010;10:429. DOI: 10.1186/1471-2407-10-429. PMID: 20712874.Li F. Q., Liu Q., Han Y. L. et al. Sperm protein 17 is highly expressed in endometrial and cervical cancers. BMC Cancer 2010;10:429. DOI: 10.1186/1471-2407-10-429. PMID: 20712874.Demento S. L., Siefert A. L., Bandyopadhyay A. et al. Pathogenassociated molecular patterns on biomaterials: a paradigm for engineering new vaccines. Trends Biotechnol 2011;29(6):294–306. DOI: 10.1016/j.tibtech.2011.02.004. PMID: 21459467.Demento S. L., Siefert A. L., Bandyopadhyay A. et al. Pathogenassociated molecular patterns on biomaterials: a paradigm for engineering new vaccines. Trends Biotechnol 2011;29(6):294–306. DOI: 10.1016/j.tibtech.2011.02.004. PMID: 21459467.Forghanifard M. M., Gholamin M., Farshchian M. et al. Cancer-testisgene expression profiling in esophageal squamous cell carcinoma: identificationof specific tumor marker and potential targets for immunotherapy. Cancer Biol Ther 2011;12(3):191–7. PMID: 21613820.Gaugler B., van den Eynde B., van der Bruggen P. et al. Human gene MAGE-3 codes for an antigen recognized on a melanoma by autologous cytolytic T lymphocytes. J Exp Med 1994;179(3):921–30. PMID: 8113684.Ng А.К. Diffuse large B-cell lymphoma. Semin Radiat Oncol 2007;17(3):169–75. DOI: 10.1016/j.semradonc.2007.02.002. PMID: 17591563.Ng А.К. Diffuse large B-cell lymphoma. Semin Radiat Oncol 2007;17(3):169–75. DOI: 10.1016/j.semradonc.2007.02.002. PMID: 17591563.Weigert O., Unterhalt M., Hiddemann W., Dreyling M. Current man-agement of mantle cell lymphoma. Drugs 2007;67(12):1689–702. PMID: 17683170.Richardson P. G., Mitsiades C., Schlossman R. et al. New drugs for myeloma. Oncologist 2007;12(6):664–89. DOI: 10.1634/theoncologist.12-6-664. PMID: 17602058.Richardson P. G., Mitsiades C., Schlossman R. et al. New drugs for myeloma. Oncologist 2007;12(6):664–89. DOI: 10.1634/theoncologist.12-6-664. PMID: 17602058.Harris N. L., Jaffe E. S., Diebold J. et al. The World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. Report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November, 1997. Ann Oncol 1999;10(12):1419–32. PMID: 10643532.Veelken H., Osterroth F. Vaccination strategies in the treatment of lymphomas. Oncology 2002;62(3):187–200. DOI: 10.1159/000059565. PMID: 12065865.Veelken H., Osterroth F. Vaccination strategies in the treatment of lymphomas. Oncology 2002;62(3):187–200. DOI: 10.1159/000059565. PMID: 12065865.Bogen B., Ruffini P. A., Corthay A. et al. Idiotype-specific immu-notherapy in multiple myeloma: suggestions for future directions of research. Haematologica 2006;91(7):941–8. PMID: 16818282.Bogen B., Ruffini P. A., Corthay A. et al. Idiotype-specific immu-notherapy in multiple myeloma: suggestions for future directions of research. Haematologica 2006;91(7):941–8. PMID: 16818282.Richardson P. G., Sonneveld P., Schuster M. et al. Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-toevent results of the APEX trial. Blood 2007;110(10): 3557–60. DOI: 10.1182/blood-2006-08-036947. PMID: 17690257.Engelhardt M., Udi J., Kleber M. et al. European myeloma network: the 3rd Trialist forum consensus statement from the European experts meeting on multiple myeloma. Leuk Lymphoma 2010;51(11):2006–11. DOI: 10.3109/10428194.2010.516378. PMID: 20807087.Kono K., Mizukami Y., Daigo Y. et al. Vaccination with multiple peptides derived from novel cancer-testis antigens can induce specific T cell responses and clinical responses in advanced esophageal cancer. Cancer Sci 2009;100(8):1502–9.Barlogie B., Shaughnessy J., Tricot G. et al. Treatment of multiple myeloma. Blood 2004;103(1):20–32. DOI: 10.1182/blood-2003-04-1045. PMID: 12969978.Barlogie B., Shaughnessy J., Tricot G. et al. Treatment of multiple myeloma. Blood 2004;103(1):20–32. DOI: 10.1182/blood-2003-04-1045. PMID: 12969978.Bakkus M. H., Bouko Y., Samson D. et al. Post-transplantation tumour load in bone marrow, as assessed by quantitative ASOPCR, is a prognostic parameter in multiple myeloma. Br J Haematol 2004; 126(5):665–74. DOI: 10.1111/j.1365-2141.2004.05120.x. PMID: 15327517.Bakkus M. H., Bouko Y., Samson D. et al. Post-transplantation tumour load in bone marrow, as assessed by quantitative ASOPCR, is a prognostic parameter in multiple myeloma. Br J Haematol 2004; 126(5):665–74. DOI: 10.1111/j.1365-2141.2004.05120.x. PMID: 15327517.van Rhee F., Szmania S. M., Zhan F. et al. NY-ESO-1 is highly expressed in poorprognosis multiple myeloma and induces spontaneous humoral and cellular immune responses. Blood 2005;105(10):3939–44. DOI: 10.1182/blood-2004-09-3707. PMID: 15671442.van Rhee F., Szmania S. M., Zhan F. et al. NY-ESO-1 is highly expressed in poorprognosis multiple myeloma and induces spontaneous humoral and cellular immune responses. Blood 2005;105(10):3939–44. DOI: 10.1182/blood-2004-09-3707. PMID: 15671442.van Duin M., Broy A., de Knegt Y. et al. Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy. Haematologica 2011;96(11):1662–9. DOI: 10.3324/haematol.2010.037978. PMID: 21791470.