Протеомные исследования, направленные на поиск маркеров рака молочной железы (обзор литературы)

Злокачественные новообразования молочной железы занимают лидирующее место в структуре онкологических заболеваний женщин в мире. Используемые в настоящее время методы инструментальной диагностики рака молочной железы (РМЖ) и связанные с ними диагностические процедуры не являются совершенными. Общим ограничением инструментальных методов является неоднозначность интерпретации результатов, связанная с многообразием индивидуальных особенностей строения и морфологией молочной железы. Необходимы поиски новых методов диагностики и онкомаркеров, обладающих высокой специфичностью, чувствительностью, низкой стоимостью и позволяющих выявлять ранние стадии развития опухолевого процесса. По нашему мнению, перспективным и актуальным направлением в онкологии представляется поиск биомаркеров РМЖ. Масс-спектрометрические методы используются для обнаружения и идентификации протеомных маркеров в крови, биологических жидкостях, опухолевой ткани, лизатах и секретомах линий опухолевых клеток. Современное использование высокотехнологичных протеомных и масс-
спектрометрических методов исследования ориентировано на анализ биологических жидкостей и крови в целях идентификации новых биомаркеров. Действительно, анализ крови на биомаркеры не требует материала, полученного непосредственно из опухолевой ткани, а значит, не зависит от локализации опухоли, подразумевает раннее выявление первичных опухолей или вторичных очагов, и востребован в современной клинической практике врача-онколога. Представленный обзор посвящен анализу современных методов диагностики и оценки эффективности проводимой терапии РМЖ с использованием протеомных маркеров и самых последних достижений клинической онкопротеомики.

1. Заболеваемость злокачественными новообразованиями населения России и стран СНГ в 2008 году. Под ред. М. И. Давыдова, Е. М. Аксель. Вестник РОНЦ им. Н. Н. Блохина РАМН 2010;(21):52–86. [The incidence of malignant neoplasms of the people of Russia and CIS countries in 2008. Ed. by M. I. Davydova, A. M. Axel. Vestnik RONC im. N. N. Blokhina RAMN = Bulletin of N. N. Blokhin RCRC of RAMS 2010;(21):52–86. (In Russ.)].

2. Greenlee R. T., Murray T., Bolden S., Wingo P. A. Cancer statistics, 2000. CA Cancer J Clin 2000;50(1):7–33.

3. Matsuda T., Saika K. Worldwide burden of cancer incidence in 2002 extrapolated from cancer incidence in five continents. Vol. IX. Jpn J Clin Oncol 2012;42(11):1111–2.

4. World cancer report 2008. International agency for research on cancer. Lyon, 2008. P. 64.

5. Пак Д. Д., Сарибекян Э. К. Опухоли молочной железы. Руководство по онкологии. Под ред. С. Л. Дарьяловой. М., 2008, С. 342–408. [Pak D. D., Saribekyan E. K. Mammary tumors. Oncology guideline. Ed. by S. L. Daryalova. Moscow, 2008. Pp. 342–408. (In Russ.)].

6. Тамкович С. Н., Войцицкий В. Е., Лактионов П. П. Cовременные методы диагностики рака молочной железы. Биомедицинская химия 2014;60(2):141–60. [Tamkovich S. N., Voitsitsky V. E., Laktionov P. P. Modern methods of breast cancer diagnostics. Biomeditsinskaya khimiya = Biomedical Chemistry 2014;60(2):141–60. (In Russ.)].

7. Popiel M., Mroz-Klimas D., Kasprazak R., Furmanek M. Mammary carcinoma – current diagnostic methods and symptomatology in imaging studies. Pol J Radiol 2012;77(4):35–44.

8. Бухарин Д. Г., Величко С. А., Фролова И. Г., Лунева С. В. Ультрасонография и рентгеновская маммография в диагностике рака молочной железы, развившегося на фоне мастопатии. Сибирский онкологический журнал 2012;27(1):99–102. [Bukharin D. G., Velichko S. A., Frolova I. G., Luneva S. V. Ultrasonography and x-ray mammography in the diagnosis of breast cancer, developed on the background of mastitis. Sibirskiy onkologicheskiy zhurnal = Siberian Journal of Oncology 2012;27(1):99– 102. (In Russ.)].

9. Серебрякова С. В., Труфанов Г. Е., Юхно Е. А. Магнитно-резонансная семиотика. Опухоли женской репродуктивной системы 2009;(3–4):20–5. [Serebryakova S.V., Trufanov G. E., Yukhno E. A. Magnetic resonance semiotics breast cancer. Opukholi zhenskoy reproduktivnoy sistemy = Tumors of Woman ,

10. s Reproductive System 2009;(3–4): 20–5. (In Russ.)].

11. Popiela T. J., Kibil W., Herman-Sucharska I., Urbanik A. The use of magnetic resonance mammography in women at increased risk for developing breast cancer. Wideochir Inne Tech Maloinwazyjne 2013;8(1):55–62.

12. Lee I. H., Sohn M., Lim H. J. et al. Ahnak functions as a tumor suppressor via modulation of TGFβ/Smad signaling pathway. Oncogene 2014;33(38):4675–84.

13. Leong S., Nunez A. C., Lin M. Z. et al. iTRAQ-based proteomic profiling of breast cancer cell response to doxorubicin and TRAIL. J Proteome Res 2012;11(7):3561–72.

14. Ivanović V., Todorović-Raković N., Demajo M. et al. Elevated plasma levels of transforming growth factor-beta1 (TGF-β1) in patients with advanced breast cancer: association with disease progression. Eur J Cancer 2003;39(4):454–61.

15. Zeng C., Ke Z., Song Y. et al. Annexin A3 is associated with a poor prognosis in breast cancer and participates in the modulation of apoptosis in vitro by affecting the Bcl-2/Bax balance. Exp Mol Pathol 2013;95(1):23–31.

16. Dhakal H. P., Naume B., Synnestvedt M. et al. Expression of cyclooxygenase-2 in invasive breast carcinomas and its prognostic impact. Histol Histopathol 2012;27(10):1315–25.

17. Sui W., Zhang Y., Wang Z. et al. Antitumor effect of a selective COX-2 inhibitor, celecoxib, may be attributed to angiogenesis inhibition through modulating the PTEN/PI3K/Akt/ HIF-1 pathway in an H22 murine hepatocarcinoma model. Oncol Rep 2014;31(5):2252–60.

18. Díaz-Chávez J., Fonseca-Sánchez M. A., Arechaga-Ocampo E. et al. Proteomic profiling reveals that resveratrol inhibits HSP27 expression and sensitizes breast cancer cells to doxorubicin therapy. PLoS One 2013;8(5):e64378.

19. Acunzo J., Andrieu C., Baylot V. et al. Hsp27 as a therapeutic target in cancers. Curr Drug Targets 2014;15(4):423–31.

20. McConnell J.R., McAlpine S. R. Heat shock proteins 27, 40, and 70 as combinational and dual therapeutic cancer targets. Bioorg

21. Med Chem Lett 2013;23(7):1923–8.

22. Wang X., Chen M., Zhou J., Zhang X. HSP27, 70 and 90, anti-apoptotic proteins, in clinical cancer therapy (Review). Int J Oncol 2014;45(1):18–30.

23. Simpson N. E., Lambert W. M., Watkins R. et al. High levels of Hsp90 cochaperone p23 promote tumor progression and poor prognosis in breast cancer by increasing lymph node metastases and drug resistance. Cancer Res 2010;70(21):8446–56.

24. Amoroso M. R., Matassa D. S., Laudiero G. et al. TRAP1 and the proteasome regulatory particle TBP7/Rpt3 interact in the endoplasmic reticulum and control cellular ubiquitination of specific mitochondrial proteins. Cell Death Differ 2012;19(4): 592–04.

25. Tsai C. L., Tsai C. N., Lin C. Y. et al. Secreted stress-induced phosphoprotein 1 activates the ALK2-SMAD signaling pathways and promotes cell proliferation of ovarian cancer cells original research article. Cell Rep 2012;2(2):283–93.

26. Bonuccelli G., Castello-Cros R., Capozza F. et al. The milk protein-casein functions as a tumor suppressor via activation of STAT1 signaling, effectively preventing breast cancer tumor growth and metastasis. Cell Cycle 2012;11(21):3972–82.

27. Jin Q., Yuan L. X., Boulbes D. et al. Fatty acid synthase phosphorylation: a novel therapeutic target in HER2- verexpressing breast cancer cells. Breast Cancer Res 2010;12(6):R96.

28. Ishimura N., Amano Y., Sanchez-Siles A. A. et al. Fatty acid synthase expression in Barrett’s esophagus: implications for carcinogenesis. J Clin Gastroenterol 2011;45(8):665–72.

29. Li J. Q., Xue H., Zhou L. et al. Mechanism of fatty acid synthase in drug tolerance related to epithelial-mesenchymal transition of breast cancer. Asian Pac J Cancer Prev 2014;15(18): 7617–23.

30. Niemantsverdriet M., Wagner K., Visser M., Backendorf C. Cellular functions of 14-3-3 zeta in apoptosis and cell adhesion emphasize its oncogenic character. Oncogene 2008;27(9):1315–9.

31. Lu J., Guo H., Treekitkarnmongkol W. et al. 14-3-3 zeta cooperates with ErbB2 to promote ductal carcinoma in situ progression to invasive breast cancer by inducing epithelialmesenchymal transition. Cancer Cell 2009;16(3):195–207.

32. Neal C. L., Yao J., Yang W. et al. 14-3-3zeta overexpression defines high risk for breast cancer recurrence and promotes cancer cell survival. Cancer Res 2009;69(8):3425–32.

33. Neal C. L., Xu J., Li P. et al. Overexpression of 14-3-3ζ in cancer cells activates PI3K via binding the p85 regulatory subunit. Oncogene 2012;31(7):897–906.

34. Qi W. Overexpression of 14-3-3gamma causes polyploidization in H322 lung cancer cells. Mol Carcinog 2007;46(10):847–56.

35. Jin Y. H., Kim Y. J., Kim D. W. et al. Sirt2 interacts with 14-3-3 beta/gamma and downregulates the activity of p53. Biochem Biophys Res Commun 2008;368(3):690–5.

36. Radhakrishnan V. M., Martinez J. D. 14-3-3gamma induces oncogenic transformation by stimulating MAP kinase and PI3K signaling. PLoS One 2010;5(7):11433.

37. Li Y., Inoki K., Yeung R., Guan K. L. Regulation of TSC2 by 14-3-3 binding. J Biol Chem 2002;277(47):44593–6.

38. Chen H., Liu L., Ma B. Protein kinase Amediated 14-3-3 association impedes human dapper1 to promote dishevelled degradation. J Biol Chem 2011;286(17):14870–80.

39. Kartiki V. Desai, S100A6 as a biomarker in human breast cancer. Proc Amer Assoc Cancer Res 2005;46:448.

40. Al-Haddad S., Zhang Z., Leygue E. et al. Psoriasin (S100A7) expression and invasive breast cancer. Am J Pathol 1999;155(6): 2057–66.

41. Moon A., Yong H. Y., Song J. I. et al. Global gene expression profiling unveils, S100A8/A9 as candidate markers in H-asmediated human breast epithelial cell invasion. Mol Cancer Res 2008;6(10):1544–53.

42. Li C., Chen H., Ding F. et al. A novel p53 target gene, S100A9, induces p53-dependent cellular apoptosis and mediates the p53 apoptosis pathway. Biochem J 2009;422(2):363–72.

43. Zhang J., Guo B., Zhang Y. et al. Silencing of the annexin II gene down-regulates the levels of S100A10, c-Myc, and plasmin and inhibits breast cancer cell proliferation and invasion. Saudi Med J 2010;31(4):374–81.

44. McKiernan E., McDermott E.W., Evoy D. et al. The role of S100 genes in breast cancer progression. Tumour Biol 2011;32(3):441–50.

45. Søiland H., Skaland I., Janssen E. A. et al. Comparison of apolipoprotein D determination methods in breast cancer. Anticancer Res 2008;28(2B):1151–60.

46. Zelco I. N., Mariani T. J., Folz R. J. Superoxide dismutase multigene family: а comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution and expression. Free Radic Biol Med 2002;33(3):337–49.

47. Rinaldi S., Peeters P. H., Berrino F. IGF-I, IGFBP-3 and breast cancer risk in women: The European Prospective Investigation nto Cancer and Nutrition (EPIC). Endocr Relat Cancer 2006;13(2):593–605.

48. Suzuki T., Urano T., Tsukui T. et al. Estrogen-responsive finger protein as a new potential biomarker for breast cancer. Clin Cancer Res 2005;11(17):6148–54.

49. Ko S., Kim J. Y., Jeong J. et al. The role and regulatory mechanism of 14-3-3 sigma in human breast cancer. J Breast Cancer 2014;17(3):207–18.

50. Liu X. G., Wang X. P., Li W. F. et al. Ca2+-binding protein S100A11: a novel diagnostic marker for breast carcinoma. Oncol Rep 2010;23(5):1301–8.

51. Zhao H., Ou-Yang F., Chen I. F. et al. Enhanced resistance to tamoxifen by the c-ABL proto-oncogene in breast cancer. Neoplasia 2010;12(3):214–23.

52. Chen S. T., Pan T. L., Tsai Y. C., Huang C. M. Proteomics reveals protein profile changes in doxorubicin – treated MCF-7 human breast cancer cells. Cancer Lett 2002;181(1):95–107.

53. Kumbrink J., Kirsch K. H. Regulation of p130Cas/BCAR1 expression in tamoxifensensitive and tamoxifen-resistant breast cancer cells by EGR1 and NAB2. Neoplasia 2012;14(2):108–20.

54. Leong S., McKay M.J., Christopherson R. I., Baxter R. C. Biomarkers of breast cancer apoptosis induced by chemotherapy and TRAIL. J Proteome Res 2012;11(2):1240–50.

55. Kabir N. N., Rönnstrand L., Kazi J. U. Keratin 19 expression correlates with poor prognosis in breast cancer. Mol Biol Rep 2014;41(12):7729–35.

56. Singh B., Cook K. R., Vincent L. et al. Role of COX-2 in tumorospheres derived from a breast cancer cell line. J Surg Res

57. ;168(1):39–49.

58. Tymoszuk P., Charoentong P., Hackl H. et al. High STAT1 mRNA levels but not its tyrosine phosphorylation are associated with macrophage infiltration and bad prognosis in breast cancer. BMC Cancer 2014;14:257.

59. Huang R., Faratian D., Sims A. H. et al. Increased STAT1 signaling in endocrine- resistant breast cancer. PLoS One 2014;9(4):e94226.

60. Wang M., Wang Y., Zhong J. Side population cells and drug resistance in breast cancer. Mol Med Rep 2015;11(6):4297–302.

61. Bensimon J., Biard D., Paget V. et al. Forced extinction of CD24 stem-like breast cancer marker alone promotes radiation resistance through the control of oxidative stress. Mol Carcinog 2015.

62. Koziel J. E., Herbert B. S. The telomerase inhibitor imetelstat alone, and in combination with trastuzumab, decreases the cancer stem cell population and self-renewal of HER2⁺ breast cancer cells. Breast Cancer Res Treat 2015;149(3):607–18.

63. Lamb R., Ozsvari B., Lisanti C. L. et al. Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: treating cancer like an infectious disease. Oncotarget 2015;6(7):4569–84.

64. Assefnia S., Dakshanamurthy S., Guidry Auvil J. M. et al. Cadherin-11 in poor prognosis malignancies and rheumatoid rthritis: common target, common therapies. Oncotarget 2014;5(6):1458–74.

65. Lim J. C., Koh V. C., Tan J. S. et al. Prognostic significance of epithelial-mesenchymal transition proteins Twist and Foxc2 in phyllodes tumours of the breast. Breast Cancer Res Treat 2015;150(1):19–29.

66. Ha S. A., Lee Y. S., Kim H. K. et al. The prognostic potential of keratin 18 in breast cancer associated with tumor dedifferentiation, and the loss of estrogen and progesterone receptors. Cancer Biomark 2011;10(5):219–31.

67. Kumar R., Kumar A. N., Srivastava A. Breast cancer tumor markers. J Sol Tum 2012;2(1):43–6.

68. Shaheed S. U., Rustogi N., Scally A. et al. Identification of stage-specific breast markers using quantitative proteomics. J Proteome Res 2013;12(12):5696–708.

69. Zhang B., Ma X., Li Z. et al. Celecoxib enhances the efficacy of 15-hydroxyprostaglandin dehydrogenase gene therapy in treating

70. murine breast cancer. J Cancer Res Clin Oncol 2013;139(5):797–807.