Predictive biomarkers in the treatment of acromegaly: a review of the literature

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Abstract


In the era of personalized medicine treatment of acromegaly requires the individual selection of optimal treatment based on the measured parameters. Following the standard algorithm for the management of patients with acromegaly with the choice of neurosurgical treatment as the main and somatostatin analogues as the first line of drug therapy with ineffective surgery prevents the achievement of remission in patients resistant to these types of therapy. The introduction of predictive biomarkers in clinical practice will allow to achieve remission of the disease faster and reduce the financial costs of ineffective treatments. We collected information of possible predictive biomarkers in acromegaly from literature. This review presents data from studies of potential predictive biomarkers in different treatments of acromegaly. According to the analysis of publications, the greatest number of results is devoted to the prediction resistance to somatostatin analogues. Reliable biomarkers predicting the inefficiency of somatostatin analogues include low immunoexpression of somatostatin receptors type 2 and AIP protein, rarely granular type of pituitary adenoma and hyperintensive signal on T2-weighted images in magnetic resonance imaging of the pituitary gland. At the same time, the search for predictors of the effectiveness of pegvisomant is focused on the study of the receptor of growth hormone and opens up new opportunities for pharmacogenomic research. Thus, it is necessary to expand the search of predictive biomarkers for different methods of acromegaly’s treatment. It is especially important to identify biomarkers that do not require mandatory removal of the tumor. Of great interest is the study of epigenetic biomarkers, in particular miRNAs, which carry out post-transcriptional regulation of gene expression. The study of circulating blood microRNAs in acromegaly opens up prospects for the introduction of a personalized approach in the treatment of this disease.


E. G. Przhiyalkovskaya

Endocrinology Research Centre

Email: przhiyalkovskaya.elena@gmail.com
ORCID iD: 0000-0001-9119-2447
SPIN-code: 9309-3256

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

MD, PhD

Patimat O. Osmanova

Endocrinology Research Centre

Author for correspondence.
Email: osmanova.ne@yandex.ru
ORCID iD: 0000-0003-0473-8144
SPIN-code: 8179-7602

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

Elizaveta O. Mamedova

Endocrinology Research Centre

Email: lilybet@mail.ru
ORCID iD: 0000-0002-9783-3599
SPIN-code: 3904-6017

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

MD, PhD

Alexander S. Lutsenko

Endocrinology Research Centre

Email: some91@mail.ru
ORCID iD: 0000-0002-9314-7831
SPIN-code: 4037-1030

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

Zhanna E. Belaya

Endocrinology Research Centre

Email: jannabelaya@gmail.com
ORCID iD: 0000-0002-6674-6441
SPIN-code: 4746-7173

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

MD, PhD

Galina A. Melnichenko

Endocrinology Research Centre

Email: Teofrast2000@mail.ru
ORCID iD: 0000-0002-5634-7877
SPIN-code: 8615-0038

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

MD, PhD, Professor

  1. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69(3):89–95. doi: 10.1067/mcp.2001.113989.
  2. Katznelson L, Laws ER, Melmed S, et al. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(11):3933–3951. doi: 10.1210/jc.2014-2700.
  3. Kasuki L, Wildemberg LE, Gadelha MR. Management of endocrine disease: personalized medicine in the treatment of acromegaly. Eur J Endocrinol. 2018;178(3):R89–R100. doi: 10.1530/eje-17-1006.
  4. Holdaway IM, Bolland MJ, Gamble GD. A meta-analysis of the effect of lowering serum levels of GH and IGF-I on mortality in acromegaly. Eur J Endocrinol. 2008;159(2):89–95. doi: 10.1530/eje-08-0267.
  5. Ben-Shlomo A, Melmed S. Acromegaly. Endocrinol Metab Clin North Am. 2008;37(1):101–122. doi: 10.1016/j.ecl.2007.10.002.
  6. Nomikos P, Buchfelder M, Fahlbusch R. The outcome of surgery in 668 patients with acromegaly using current criteria of biochemical “cure.” Eur J Endocrinol. 2015;152(3):379–387. doi: 10.1530/eje.1.01863.
  7. Fathalla H, Cusimano MD, Di Ieva A, et al. Endoscopic versus microscopic approach for surgical treatment of acromegaly. Neurosurg Rev. 2015;38(3):541–549. doi: 10.1007/s10143-015-0613-7.
  8. Giustina A, Chanson P, Kleinberg D, et al. Expert consensus document: a consensus on the medical treatment of acromegaly. Nat Rev Endocrinol. 2014;10(4):243–248. doi: 10.1038/nrendo.2014.21.
  9. Buchfelder M, Schlaffer SM. The surgical treatment of acromegaly. Pituitary. 2016;20(1):76–83. doi: 10.1007/s11102-016-0765-7.
  10. Cohen-Gadol AA, Liu JK, Laws ER. Cushing’s first case of transsphenoidal surgery: the launch of the pituitary surgery era. J Neurosurg. 2015;103(3):570–574. doi: 10.3171/jns.2005.103.3.0570.
  11. Григорьев А.Ю., Азизян В.Н., Иващенко О.В., и др. Результаты хирургического лечения соматотропных аденом гипофиза // Эндокринная хирургия. ― 2008. ― Т.2. ― №1. ― C. 6–9. [Grigor'ev AYu, Azizyan VN, Ivashchenko OV, et al. Rezul'taty khirurgicheskogo lecheniya somatotropnykh adenom gipofiza. Endokrinnaia khirurgiia. 2008;2(1):6–9. (In Russ).]
  12. Pless J. The history of somatostatin analogs. J Endocrinol Invest. 2005;28(11 Suppl International):1−4.
  13. Melmed S, Bronstein MD, Chanson P, et al. A Consensus statement on acromegaly therapeutic outcomes. Nat Rev Endocrinol. 2018;14(9):552–561. doi: 10.1038/s41574-018-0058-5.
  14. Paragliola RM, Corsello SM, Salvatori R. Somatostatin receptor ligands in acromegaly: clinical response and factors predicting resistance. Pituitary. 2016;20(1):109–115. doi: 10.1007/s11102-016-0768-4.
  15. Марова Е.И., Мельниченко Г.А., Кадашев Б.А., и др. Медикаментозное лечение акромегалии: результаты длительного применения Cандостатина ЛАР // Проблемы эндокринологии. ― 2006. ― Т.52. ― №4. ― С. 34–38. [Marova EI, Mel’nichenko GA, Kadashev BA, et al. Drug treatment for acromegaly: results of long-term use of Sandostatin LAR. Problemy endokrinologii. 2006;52(4):34–38. (In Russ).]
  16. Colao A, Auriemma RS, Pivonello R, et al. Interpreting biochemical control response rates with first-generation somatostatin analogues in acromegaly. Pituitary. 2015;19(3):235–247. doi: 10.1007/s11102-015-0684-z.
  17. Suda K, Inoshita N, Iguchi G, et al. Efficacy of combined octreotide and cabergoline treatment in patients with acromegaly: a retrospective clinical study and review of the literature. Endocr J. 2013;60(4):507−515. doi: 10.1507/endocrj.ej12-0272.
  18. Sandret L, Maison P, Chanson P. Place of cabergoline in acromegaly: a meta-analysis. J Clin Endocrinol Metab. 2011;96(5):1327–1335. doi: 10.1210/jc.2010-2443.
  19. Neggers SJ, Franck SE, de Rooij FW, et al. Long-term efficacy and safety of pegvisomant in combination with long-acting somatostatin analogs in acromegaly. J Clin Endocrinol Metab. 2014;99(10):3644–3652. doi: 10.1210/jc.2014-2032.
  20. Gadelha MR, Bronstein MD, Brue T, et al. Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial. Lancet Diab Endocrinol. 2014;2(11):875–884. doi: 10.1016/s2213-8587(14)70169-x.
  21. Пржиялковская Е.Г., Абросимов А.Ю., Григорьев А.Ю., и др. Прогностическое значение экспрессии Ki-67, CD31 и VEGF в соматотропиномах // Архив патологии. ― 2010. ― Т.72. ― №1. ― С. 35–38. [Przhiyalkovskaya EG, Abrosimov AYu, Grigor’ev AYu, et al. Prognosticheskoe znachenie ekspressii Ki-67, CD31 i VEGF v somatotropinomakh. Arkhiv patologii. 2010;72(1):35–38. (In Russ).]
  22. Ramos-Leví AM, Bernabeu I, Sampedro-Núñez M, et al. Genetic predictors of response to different medical therapies in acromegaly. Prog Mol Biol Transl Sci. 2016;138:85−114. doi: 10.1016/bs.pmbts.2015.10.016
  23. Akin F, Turgut S, Cirak B, et al. IGF(CA)19 and IGFBP-3-202A/C gene polymorphism in patients with acromegaly. Grow Hormon IGF Res. 2010;20(6):399–403. doi: 10.1016/j.ghir.2010.09.001.
  24. Larkin S, Reddy R, Karavitaki N, et al. Granulation pattern, but not GSP or GHR mutation, is associated with clinical characteristics in somatostatin-naïve patients with somatotroph adenomas. Eur J Endocrinol. 2013;168(4):491–499. doi: 10.1530/eje-12-0864.
  25. Fougner SL, Casar‐Borota O, Heck A, et al. Adenoma granulation pattern correlates with clinical variables and effect of somatostatin analogue treatment in a large series of patients with acromegaly. Clin Endocrinol. 2012;76:96−102. doi: 10.1111/j.1365-2265.2011.04163.x.
  26. Shen M, Zhang Q, Liu W, et al. Predictive value of T2 relative signal intensity for response to somatostatin analogs in newly diagnosed acromegaly. Neuroradiol. 2016;58(11):1057–1065. doi: 10.1007/s00234-016-1728-4.
  27. Heck A, Emblem KE, Casar-Borota O, et al. Quantitative analyses of T2-weighted MRI as a potential marker for response to somatostatin analogs in newly diagnosed acromegaly. Endocrin. 2015;52(2):333–343. doi: 10.1007/s12020-015-0766-8.
  28. Gatto F, Feelders RA, van der Pas, et al. Immunoreactivity score using an anti-sst2A receptor monoclonal antibody strongly predicts the biochemical response to adjuvant treatment with somatostatin analogs in acromegaly. J Clin Endocrinol Metab. 2013;98(1):E66–E71. doi: 10.1210/jc.2012-2609.
  29. Wildemberg LE, Neto LV, Costa DF, et al. Low somatostatin receptor subtype 2, but not dopamine receptor subtype 2 expression predicts the lack of biochemical response of somatotropinomas to treatment with somatostatin analogs. J Endocrinol Invest. 2013;36(1):38–43. doi: 10.3275/8305.
  30. Durán-Prado M, Saveanu A, Luque RM, et al. A potential inhibitory role for the new truncated variant of somatostatin receptor 5, sst5TMD4, in pituitary adenomas poorly responsive to somatostatin analogs. J Clin Endocrinol Metab. 2010;95(5):2497–2502. doi: 10.1210/jc.2009-2247.
  31. Córdoba-Chacón J, Gahete MD, Durán-Prado M, et al. Truncated somatostatin receptors as new players in somatostatin-cortistatin pathophysiology. Ann N Y Acad Sci. 2011;1220(1):6–15. doi: 10.1111/j.1749-6632.2011.05985.x.
  32. Neto LV, Machado Ede O, Luque RM, et al. Expression analysis of dopamine receptor subtypes in normal human pituitaries, nonfunctioning pituitary adenomas and somatotropinomas, and the association between dopamine and somatostatin receptors with clinical response to octreotide-lar in acromegaly. J Clin Endocrinol Metab. 2009;94(6):1931–1937. doi: 10.1210/jc.2008-1826.
  33. Daly AF, Tichomirowa MA, Petrossians P, et al. Clinical characteristics and therapeutic responses in patients with germ-line AIP mutations and pituitary adenomas: an international collaborative study. J Clin Endocrinol Metab. 2010;95(11):E373–E383. doi: 10.1210/jc.2009-2556.
  34. Kasuki L, Vieira Neto L, Wildemberg LE, et al. AIP expression in sporadic somatotropinomas is a predictor of the response to octreotide LAR therapy independent of SSTR2 expression. Endocr Relat Cancer. 2012;19(3):L25–L29. doi: 10.1530/erc-12-0020.
  35. Fougner SL, Bollerslev J, Latif F, et al. Low levels of raf kinase inhibitory protein in growth hormone-secreting pituitary adenomas correlate with poor response to octreotide treatment. J Clin Endocrinol Metab. 2008;93(4):1211–1216. doi: 10.1210/jc.2007-2272.
  36. Barlier A, Gunz G, Zamora AJ, et al. Pronostic and therapeutic consequences of gsα mutations in somatotroph adenomas. J Clin Endocrinol Metab. 1998;83(5):1604–1610. doi: 10.1210/jcem.83.5.4797.
  37. Kasuki L, Wildemberg LE, Neto LV, et al. Ki-67 is a predictor of acromegaly control with octreotide LAR independent of SSTR2 status and relates to cytokeratin pattern. Eur J Endocrinol. 2013;169(2):217–223. doi: 10.1530/eje-13-0349.
  38. Wang M, Shen M, He W, et al. The value of an acute octreotide suppression test in predicting short-term efficacy of somatostatin analogues in acromegaly. Endocr J. 2016;63(9):819–834. doi: 10.1507/endocrj.ej16-0175.
  39. Puig Domingo M. Treatment of acromegaly in the era of personalized and predictive medicine. Clin Endocrinol. 2015;3(1):3–14. doi: 10.1111/cen.12731.
  40. Пронин В.С., Гитель Е.П., Васильева И.В., и др. Прогностические факторы эффективности медикаментозного лечения акромегалии // Врач. ― 2010. ― №2. ― С. 39–43. [Pronin VS, Gitel’ EP, Vasil’eva IV, et al. Prognostic factors of the efficiency of medical treatment for acromegaly. Vrach. 2010;(2):39–43. (In Russ).]
  41. Dénes J, Kasuki L, Trivellin G, et al. Regulation of aryl hydrocarbon receptor interacting protein (aip) protein expression by MiR-34a in sporadic somatotropinomas. PLOS ONE. 2015;10(2): e0117107. doi: 10.1371/journal.pone.0117107.
  42. Iacovazzo D, Carlsen E, Lugli F, et al. Factors predicting pasireotide responsiveness in somatotroph pituitary adenomas resistant to first-generation somatostatin analogues: an immunohistochemical study. Eur J Endocrinol. 2016;174(2):241–250. doi: 10.1530/EJE-15-0832.
  43. Bernabeu I, Alvarez-Escolà C, Quinteiro C, et al. The exon 3-deleted growth hormone receptor is associated with better response to pegvisomant therapy in acromegaly. J Clin Endocrinol Metab. 2010;95(1):222–229. doi: 10.1210/jc.2009-1630.
  44. Bianchi A, Mazziotti G, Tilaro L, et al. Growth hormone receptor polymorphism and the effects of pegvisomant in acromegaly. Pituitary. 2009;12(3):196–199. doi: 10.1007/s11102-008-0157-8.
  45. Poon T, Leung S, Poon C, et al. Predictors of outcome following Gamma Knife surgery for acromegaly. J Neurosurg. 2010;113(Suppl):149−152. doi: 10.3171/2010.7.gks10933.
  46. Micko AS, Wöhrer A, Wolfsberger S, et al. Invasion of the cavernous sinus space in pituitary adenomas: endoscopic verification and its correlation with an MRI-based classification. J Neurosurg. 2015;122(4):803–811. doi: 10.3171/2014.12.jns141083.
  47. Pizarro CB, Oliveira MC, Coutinho LB, et al. Measurement of Ki-67 antigen in 159 pituitary adenomas using the MIB-1 monoclonal antibody. Brazil J Med Biol Res. 2004;37(2):235−243. doi: 10.1590/S0100-879X2004000200011.
  48. Costalonga EF, Antonini SRR, Guerra-Junior G, et al. Growth hormone pharmacogenetics: the interactive effect of a microsatellite in the IGF1 promoter region with the GHR-exon 3 and 202 A/C IGFBP3 variants on treatment outcomes of children with severe GH deficiency. Pharmacogenom J. 2011;12(5):439–445. doi: 10.1038/tpj.2011.13.
  49. Ramos-Leví AM, Marazuela M, Paniagua A, et al. Analysis of IGF(CA)19 and IGFBP3-202A/C gene polymorphisms in patients with acromegaly: association with clinical presentation and response to treatments. Eur J Endocrinol. 2015;172(2):115–122. doi: 10.1530/eje-14-0613.
  50. Hazer DB, Isik S, Berker D, et al. Treatment of acromegaly by endoscopic transsphenoidal surgery: surgical experience in 214 cases and cure rates according to current consensus criteria. J Neurosurg. 2013;119(6):1467–1477. doi: 10.3171/2013.8.JNS13224.
  51. Ajler P, Campero A, Landriel F, et al. Early results of microsurgical treatment of acromegaly. Int Neurosci J. 2018;2(1):22−29. doi: 10.1515/inj-2017-0004.
  52. Taboada GF, Luque RM, Neto LV, et al. Quantitative analysis of somatostatin receptor subtypes (1–5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR. Eur J Endocrinol. 2008;158(3):295–303. doi: 10.1530/EJE-07-0562.
  53. Gadelha MR, Kasuki L, Korbonits M. Novel pathway for somatostatin analogs in patients with acromegaly. Trends Endocrinol Metab. 2013;24(5):238−246. doi: 10.1016/j.tem.2012.11.007.
  54. Igreja S, Chahal HS, King P, et al. Characterization of aryl hydrocarbon receptor interacting protein (AIP) mutations in familial isolated pituitary adenoma families. Human Mutation. 2010;31(8):950–960. doi: 10.1002/humu.21292.
  55. Далантаева Н.С., Дедов И.И. Генетические и обменные особенности семейных изолированных аденом гипофиза // Ожирение и метаболизм. ― 2013. ― Т.10. ― №2. ― 3−10. [Dalantaeva NS, Dedov II. Genetic and metabolic characteristics of familial isolated pituitary adenomas. Obesity and metabolism. 2013;10(2):3−10. (In Russ).]
  56. Jaffrain-Rea ML, Angelini M, Gargano D, et al. Expression of aryl hydrocarbon receptor (AHR) and AHR-interacting protein in pituitary adenomas: pathological and clinical implications. Endocr Relat Cancer. 2009;16(3):1029–1043. doi: 10.1677/erc-09-0094.
  57. Venegas‐Moreno E, Flores‐Martinez A, Dios E, et al. E‐cadherin expression is associated with somatostatin analogue response in acromegaly. J Cell Mol Med. 2019;23(5):3088−3096. doi: 10.1111/jcmm.13851.
  58. Gatto F, Feelders R, van der Pas, et al. β-arrestin 1 and 2 and G protein-coupled receptor kinase 2 expression in pituitary adenomas: role in the regulation of response to somatostatin analogue treatment in patients with acromegaly. Endocrinol. 2013;154(12):4715–4725. doi: 10.1210/en.2013-1672.
  59. Puig-Domingo M, Resmini E, Gomez-Anson B, et al. Magnetic resonance imaging as a predictor of response to somatostatin analogs in acromegaly after surgical failure. J Clin Endocrinol Metab. 2010;95(11):4973–4978. doi: 10.1210/jc.2010-0573.
  60. De Herder WW, Taal HR, Uitterlinden P, et al. Limited predictive value of an acute test with subcutaneous octreotide for long-term IGF-I normalization with Sandostatin LAR in acromegaly. Eur J Endocrinol. 2005;153(1):67–71. doi: 10.1530/eje.1.01935.
  61. Eden Engstrom B, Burman P, Karlsson FA. Men with acromegaly need higher doses of octreotide than women. Clin Endocrinol. 2002;56(1):73–77. doi: 10.1046/j.0300-0664.2001.01440.x.
  62. Newman CB, Melmed S, Snyder PJ, et al. Safety and efficacy of long-term octreotide therapy of acromegaly: results of a multicenter trial in 103 patients ― a clinical research center study. J Clin Endocrinol Metab. 1995;80(9):2768–2775. doi: 10.1210/jcem.80.9.7673422.
  63. Ferone D, de Herder WW, Pivonello R, et al. Correlation ofin vitroandin vivo somatotropic adenoma responsiveness to somatostatin analogs and dopamine agonists with immunohistochemical evaluation of somatostatin and dopamine receptors and electron microscopy. J Clin Endocrinol Metab. 2008;93(4):1412–1417. doi: 10.1210/jc.2007-1358.
  64. Cozzi R, Attanasio R, Lodrini S, et al. Cabergoline addition to depot somatostatin analogues in resistant acromegalic patients: efficacy and lack of predictive value of prolactin status. Clin Endocrinol. 2004;61(2):209–215. doi: 10.1111/j.1365-2265.2004.02082.x.
  65. Marova EI, Lyulieva EG, Abrosimov AY, et al. Immunohistochemistry for dopamine receptor type 2 in pituitary adenomas in acromegalic patients. Proceedings of the 13th Congress of the European Neuroendocrine Association; Oct 17−20. Antalya, Turkey; 2008.
  66. Sherlock M, Fernandez-Rodriguez E, Alonso AA, et al. Medical therapy in patients with acromegaly: predictors of response and comparison of efficacy of dopamine agonists and somatostatin analogues. J Clin Endocrinol Metab. 2009;94(4):1255–1263. doi: 10.1210/jc.2008-1420.
  67. Pantel J, Machinis K, Sobrier ML, et al. Species-specific alternative splice mimicry at the growth hormone receptor locus revealed by the lineage of retroelements during primate evolution. J Biol Chem. 2000;275(25):18664–18669. doi: 10.1074/jbc.m001615200.
  68. Bougnères P, Goffin V. The growth hormone receptor in growth. Endocrinol Metab Clin North Am. 2007;36(1):1−16. doi: 10.1016/j.ecl.2006.08.003.
  69. Bianchi A, Giustina A, Cimino V, et al. Influence of growth hormone receptor d3 and full-length isoforms on biochemical treatment outcomes in acromegaly. J Clin Endocrinol Metab. 2009;94(6):2015–2022. doi: 10.1210/jc.2008-1337.
  70. Franck SE, van der Lely AJ, Delhanty PJ, et al. Pegvisomant in combination with long-acting somatostatin analogues in acromegaly: the role of the GH receptor deletion of exon 3. Eur J Endocrinol. 2015;173(5):553–561. doi: 10.1530/eje-15-0519.
  71. Kasuki L, Machado E de O, Ogino LL, et al. Experience with pegvisomant treatment in acromegaly in a single Brazilian tertiary reference center: efficacy, safety and predictors of response. Arch Endocr Metab. 2016;60(5):479–485. doi: 10.1590/2359-3997000000210.
  72. Filopanti M, Olgiati L, Mantovani G, et al. Growth hormone receptor variants and response to pegvisomant in monotherapy or in combination with somatostatin analogs in acromegalic patients: a multicenter study. J Clin Endocrinol Metab. 2012;97(2):E165–E172. doi: 10.1210/jc.2011-1769.
  73. Ramos-Leví AM, Bernabeu I, Sampedro-Núñez M, et al. Genetic predictors of response to different medical therapies in acromegaly Prog Mol Biol Transl Sci. 2016;138:85−114. doi: 10.1016/bs.pmbts.2015.10.016.
  74. Parkinson C, Burman P, Messig M, et al. Gender, body weight, disease activity, and previous radiotherapy influence the response to pegvisomant. J Clin Endocrinol Metab. 2007;92(1):190–195. doi: 10.1210/jc.2006-1412.
  75. Kong DS, Kim YH, Kim YH, et al. Long-term efficacy and tolerability of gamma knife radiosurgery for growth hormone-secreting adenoma: a retrospective multicenter study (MERGE-001). World Neurosurg. 2018;122:e1291−e1299. doi: 10.1016/j.wneu.2018.11.038.
  76. Ezzat S, Caspar-Bell GM, Chik CL, et al. Predictive Markers for Postsurgical Medical Management of Acromegaly: A Systematic Review and Consensus Treatment Guideline. Endocr. Pract. 2019;25(4):379-393. doi: 10.4158/ep-2018-0500
  77. Wildemberg LE, Neto LV, Costa DF, et al. Low somatostatin receptor subtype 2, but not dopamine receptor subtype 2 expression predicts the lack of biochemical response of somatotropinomas to treatment with somatostatin analogs. J Endocrinol Invest. 2013;36(1):38–43. doi: 10.3275/8305.
  78. Gatto F, Feelders RA, van der Pas R, et al. Immunoreactivity score using an anti-sst2A receptor monoclonal antibody strongly predicts the biochemical response to adjuvant treatment with somatostatin analogs in acromegaly. J Clin Endocrinol Metab. 2013;98(1):E66–E71. doi: 10.1210/jc.2012-2609.
  79. Farazi TA, Hoell JI, Morozov P, Tuschl T. MicroRNAs in human cancer. MicroRNA Adv Exp Med Biol. 2013;774:1−20. doi: 10.1007/978-94-007-5590-1_1.
  80. Chi Y, Zhou D. MicroRNAs in colorectal carcinoma ― from pathogenesis to therapy. J Exp Clin Canc Res. 2016;35:43. doi: 10.1186/s13046-016-0320-4.
  81. Khoshnevisan A, Parvin M, Ghorbanmehr N, et al. A significant upregulation of miR-886-5p in high grade and invasive bladder tumors. Urol J. 2015;12(3):2160−2164. doi: 10.22037/uj.v12i3.2222.
  82. Hunter MP, Ismail N, Zhang X, et al. Detection of microRNA expression in human peripheral blood microvesicles. PLoS ONE. 2008;3(11):e3694. doi: 10.1371/journal.pone.0003694.
  83. Michael A, Bajracharya S, Yuen P, et al. Exosomes from human saliva as a source of microRNA biomarkers. Oral Dis. 2010;16(1):34–38. doi: 10.1111/j.1601-0825.2009.01604.x.
  84. Dimov I, Velickovic LJ, Stefanovic V. Urinary exosomes. Scientific World J. 2009;9:1107–1118. doi: 10.1100/tsw.2009.128.
  85. Луценко А.С., Белая Ж.Е., Пржиялковская Е.Г., Мельниченко Г.А. МикроРНК и их значение в патогенезе СТГ-продуцирующих аденом гипофиза // Вестник РАМН. ― 2017. ― Т.72. ― №4. ― С. 290–298. [Lutsenko AS, Belaya ZE, Przhiyalkovskaya EG, Mel’nichenko GA. MicroRNA: role in GH-secreting pituitary adenoma pathogenesis. Annals of the Russian Academy of Medical Sciences. 2017;72(4):290–298. (In Russ).] doi: 10.15690/vramn856.
  86. D’Angelo D, Palmieri D, Mussnich P, et al. Altered microRNA expression profile in human pituitary gh adenomas: down-regulation of miRNA targeting HMGA1, HMGA2, and E2F1. J Clin Endocrinol Metab. 2012;97(7):1128–1138. doi: 10.1210/jc.2011-3482.
  87. Mao ZG, He DS, Zhou J, et al. Differential expression of microRNAs in GH-secreting pituitary adenomas. Diagn Pathol. 2010;5(1):79. doi: 10.1186/1746-1596-5-79.

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