Head and Neck TumorsHead and Neck TumorsОпухоли головы и шеи2222-14682411-4634Publishing House ABV Press17110.17650/2222-1468-2015-5-3-45-49ORIGINAL REPORTSОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯAssessment of diagnostic potency of exosomal microRNA in circulating blood of patient with thyroid cancerОценка диагностической роли микроРНК в составе экзосом циркулирующей крови при раке щитовидной железыSamsonovR. B.СамсоновР. Б.
Russian Federation
BurdakovV. S.БурдаковВ. С.
Russian Federation
RakitinaD. A.РакитинаД. А.
Russian Federation
NazhmudinovR. A.НажмудиновР. А.
Russian Federation
RadzhabovaZ. A.ВасильевД. А.
Russian Federation
VasilyevD. A.РаджабоваЗ. А.
Russian Federation
FilatovM. V.ФилатовМ. В.
Russian Federation
MalekA. V.МалекА. В.
Russian Federation
N. N. Petrov Research Institute of Oncology, Ministry of Health of RussiaФГБУ «НИИ онкологии им. Н. Н. Петрова» Минздрава России68 Leningradskaya St., Pesochnyi Settlement, Saint Petersburg, 197758, Russia Russian Research Center for Radiology and Surgical Technologies, Ministry of Health of RussiaРоссия, 197758, Санкт-Петербург, пос. Песочный, ул. Ленинградская, 68 ФГБУ «Российский научный центр радиологии и хирургических технологий» Минздрава России70 Leningradskaya St., Pesochnyi Settlement, Saint Petersburg, 197758, RussiaРоссия, 197758, Санкт-Петербург, пос. Песочный, ул. Ленинградская, 70National Research Center “Kurchatov Institute”, B. P. Konstantinov Saint Petersburg Institute of Nuclear PhysicsНациональный исследовательский центр «Курчатовский институт» ФГБОУ «Петербургский институт ядерной физики им. Б. П. Константинова»Orlov Roshcha, Gatchina, Leningrad Region, 188300, RussiaРоссия, 188300, Ленинградская обл., Гатчина, Орлова роща68 Leningradskaya St., Pesochnyi Settlement, Saint Petersburg, 197758, RussiaРоссия, 197758, Санкт-Петербург, пос. Песочный, ул. Ленинградская, 6868 Leningradskaya St., Pesochnyi Settlement, Saint Petersburg, 197758, Russia National Research Center “Kurchatov Institute”, B. P. Konstantinov Saint Petersburg Institute of Nuclear PhysicsРоссия, 197758, Санкт-Петербург, пос. Песочный, ул. Ленинградская, 68 Национальный исследовательский центр «Курчатовский институт» ФГБОУ «Петербургский институт ядерной физики им. Б. П. Константинова»241120155345492411201524112015Copyright ©; 2015, Samsonov R.B., Burdakov V.S., Rakitina D.A., Nazhmudinov R.A., Radzhabova Z.A., Vasilyev D.A., Filatov M.V., Malek A.V.Copyright ©; 2015, Самсонов Р.Б., Бурдаков В.С., Ракитина Д.А., Нажмудинов Р.А., Васильев Д.А., Раджабова З.А., Филатов М.В., Малек А.В.2015Samsonov R.B., Burdakov V.S., Rakitina D.A., Nazhmudinov R.A., Radzhabova Z.A., Vasilyev D.A., Filatov M.V., Malek A.V.Самсонов Р.Б., Бурдаков В.С., Ракитина Д.А., Нажмудинов Р.А., Васильев Д.А., Раджабова З.А., Филатов М.В., Малек А.В.https://creativecommons.org/licenses/by/4.0https://ogsh.abvpress.ru/jour/article/view/171

Diagnostics of thyroid cancer (TC) remains a challenging issue due to the high incidence of asymptomatic thyroid nodular pathologies and absence of non-invasive methods of their assessment. Thyroid tumors are classified as benign and malignant with incidence ration approximated as 9:1. Correct and timely differential diagnosis is the basis for correctly choosing a treatment policy and hence determines treatment results. Methods for molecular genetic analysis are being recently developed and introduced into clinical practice, enabling the diagnostic process to be optimized. Analysis of the intracellular and secreted (exosomal) fractions of small regulatory RNAs (microRNAs) is one of the most promising methods for the diagnosis of cancers, including TC. The stability of extracellular microRNA is determined by bonds to proteins, lipoproteins, or its encapsulation into the membrane microvesicles – exosomes. There is reason for suggesting that exosomes with the specific composition of microRNA are a result of the process of active and biologically important secretion while release of other microRNA forms accompanies apoptotic or necrotic cell death. This determines the special diagnostic value of the exosomal fraction of circulating microRNAs, which may reflect the presence and clinically relevant properties of a tumor. This paper discusses the state of the problem and presents methods and preliminary results of the studies conducted by the authors to develop a novel method for diagnosing and monitoring TC. Thus, level of plasma exosomal miR-21 was shown to distinguish patients with benign tumor and follicular CT, while miR-31 can help to distinguish patients with benign tumor and papillary TC. Moreover, reciprocal character of miR-21 and miR-181a concentration in plasma exosomes was detected by comparison of patient with papillary and follicular TC.

thyroidnodular goiterpapillary cancerfollicular cancermicroRNAexosomesmarkerdifferential diagnosisexpression profileщитовидная железаузловой зобпапиллярный ракфолликулярный ракмикроРНКэкзосомымаркердифференциальная диагностикапрофиль экспрессии1. Gharib H., Papina E., Paschke R. et al. American Association of Clinical Endocrinologists end Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules. Endocr Pract 2006;12(1):63–102.Gharib H., Papina E., Paschke R. et al. American Association of Clinical Endocrinologists end Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules. Endocr Pract 2006;12(1):63–102.2. Kato M.A., Fahey T.J.3rd. Molecular markers in thyroid cancer diagnostics. Surg Clin North Am 2009;89(5):1139–55.Kato M.A., Fahey T.J.3rd. Molecular markers in thyroid cancer diagnostics. Surg Clin North Am 2009;89(5):1139–55.3. Wang C.C., Friedman L., Kennedy G.C. et al. A large multicenter correlation study of thyroid nodule cytopathology and histopathology. Thyroid 2011;21(3):243–51.Wang C.C., Friedman L., Kennedy G.C. et al. A large multicenter correlation study of thyroid nodule cytopathology and histopathology. Thyroid 2011;21(3):243–51.4. Mehanna H.M., Jain A., Morton R.P. et al. Investigating the thyroid nodule. BMJ 2009;338:b733.Mehanna H.M., Jain A., Morton R.P. et al. Investigating the thyroid nodule. BMJ 2009;338:b733.5. Keutgen X.M., Filicori F., Crowley M.J. et al. A panel of four miRNAs accurately differentiates malignant from benign indeterminate thyroid lesions on fine needle aspiration. Clin Cancer Res 2012;18(7): 2032–8.Keutgen X.M., Filicori F., Crowley M.J. et al. A panel of four miRNAs accurately differentiates malignant from benign indeterminate thyroid lesions on fine needle aspiration. Clin Cancer Res 2012;18(7): 2032–8.6. Zhang Y., Zhong Q., Chen X. et al. Diagnostic value of microRNAs in discriminating malignant thyroid nodules from benign ones on fine-needle aspiration samples. Tumour Biol 2014;35(9):9343–53.Zhang Y., Zhong Q., Chen X. et al. Diagnostic value of microRNAs in discriminating malignant thyroid nodules from benign ones on fine-needle aspiration samples. Tumour Biol 2014;35(9):9343–53.7. Колесников Н.Н., Титов С.Е., Веряскина Ю.А. МикроРНК, эволюция и рак. Цитология 2013;55(3):159–64. [Kolesnikov N.N., Titov S.E., Veryaskina Yu.A. MicroRNAs, evolutions and cancer. Tsitologiya = Cytology 2013;55(3):159–64. (In Russ.)].Колесников Н.Н., Титов С.Е., Веряскина Ю.А. МикроРНК, эволюция и рак. Цитология 2013;55(3):159–64. [Kolesnikov N.N., Titov S.E., Veryaskina Yu.A. MicroRNAs, evolutions and cancer. Tsitologiya = Cytology 2013;55(3):159–64. (In Russ.)].8. Nikiforova M.N., Tseng G.C., Steward D. et al. MicroRNA expression profiling of thyroid tumors: biological significance and diagnostic utility. J Clin Endocrinol Metab 2008;93(5):1600–8.Nikiforova M.N., Tseng G.C., Steward D. et al. MicroRNA expression profiling of thyroid tumors: biological significance and diagnostic utility. J Clin Endocrinol Metab 2008;93(5):1600–8.9. Guzman N., Agarwal K., Asthagiri D. et al. Breast Cancer-Specific miR Signature Unique to Extracellular Vesicles Includes “microRNA-like” tRNA Fragments. Mol Cancer Res 2015;13(5):891–901.Guzman N., Agarwal K., Asthagiri D. et al. Breast Cancer-Specific miR Signature Unique to Extracellular Vesicles Includes “microRNA-like” tRNA Fragments. Mol Cancer Res 2015;13(5):891–901.10. Fong M.Y., Zhou W., Liu L. et al. Breastcancer-secreted miR-122 reprograms glucose metabolism in premetastatic niche to promote metastasis. Nat Cell Biol 2015;17(2):183–94.Fong M.Y., Zhou W., Liu L. et al. Breastcancer-secreted miR-122 reprograms glucose metabolism in premetastatic niche to promote metastasis. Nat Cell Biol 2015;17(2):183–94.11. Singh R., Pochampally R., Watabe K. et al. Exosome-mediated transfer of miR-10b promotes cell invasion in breast cancer. Mol Cancer 2014;13:256.Singh R., Pochampally R., Watabe K. et al. Exosome-mediated transfer of miR-10b promotes cell invasion in breast cancer. Mol Cancer 2014;13:256.12. Cereghetti D.M., Lee P.P. Tumor-Derived Exosomes Contain microRNAs with Immunological Function: Implications for a Novel Immunosuppression Mechanism. Microrna 2014;2(3):194–204.Cereghetti D.M., Lee P.P. Tumor-Derived Exosomes Contain microRNAs with Immunological Function: Implications for a Novel Immunosuppression Mechanism. Microrna 2014;2(3):194–204.13. Wei Y., Lai X., Yu S. et al. Exosomal miR-221/222 enhances tamoxifen resistance in recipient ER-positive breast cancer cells. Breast Cancer Res Treat 2014;147(2):423–31. 14. Huang X., Yuan T., Liang M. et al. Exosomal miR-1290 and miR-375 as prognostic markers in castration-resistant prostate cancer. Eur Urol 2015;67(1):33–41.Wei Y., Lai X., Yu S. et al. Exosomal miR-221/222 enhances tamoxifen resistance in recipient ER-positive breast cancer cells. Breast Cancer Res Treat 2014;147(2):423–31. 14. Huang X., Yuan T., Liang M. et al. Exosomal miR-1290 and miR-375 as prognostic markers in castration-resistant prostate cancer. Eur Urol 2015;67(1):33–41.15. Kim J., Morley S., Le M. et al. Enhanced shedding of extracellular vesicles from amoeboid prostate cancer cells: potential effects on the tumor microenvironment. Cancer Biol Ther 2014;15(4):409–18.Kim J., Morley S., Le M. et al. Enhanced shedding of extracellular vesicles from amoeboid prostate cancer cells: potential effects on the tumor microenvironment. Cancer Biol Ther 2014;15(4):409–18.16. Ogata-Kawata H., Izumiya M., Kurioka D. et al. Circulating exosomal microRNAs as biomarkers of colon cancer. PLoS One 2014;9(4):e92921.Ogata-Kawata H., Izumiya M., Kurioka D. et al. Circulating exosomal microRNAs as biomarkers of colon cancer. PLoS One 2014;9(4):e92921.17. Sato-Kuwabara Y., Melo S.A., Soares F.A., Calin G.A. The fusion of two worlds: noncoding RNAs and extracellular vesiclesdiagnostic and therapeutic implications (Review). Int J Oncol 2015;46(1):17–27.Sato-Kuwabara Y., Melo S.A., Soares F.A., Calin G.A. The fusion of two worlds: noncoding RNAs and extracellular vesiclesdiagnostic and therapeutic implications (Review). Int J Oncol 2015;46(1):17–27.18. Shtam T.A., Kovalev R.A., Varfolomeeva E.Y. et al. Exosomes are natural carriers of exogenous siRNA to human cells in vitro. Cell Commun Signal 2013;11:88.Shtam T.A., Kovalev R.A., Varfolomeeva E.Y. et al. Exosomes are natural carriers of exogenous siRNA to human cells in vitro. Cell Commun Signal 2013;11:88.