Predictive and prognostic significance of stemness gene amplifications in the breast tumor in patients who received neoadjuvant chemotherapy


如何引用文章

全文:

开放存取 开放存取
受限制的访问 ##reader.subscriptionAccessGranted##
受限制的访问 订阅或者付费存取

详细

Background. There is evidence that neoadjuvant chemotherapy (NACT) in some cases stimulates metastasis of breast cancer (BC), and the increased aggressiveness and metastasis of the tumor under the action of chemotherapy are associated with stimulation of tumor stem cells, the activity of which is determined by increased expression of stemness genes (SG). New tumor markers associated with a high risk of disease progression against the background of the treatment are required, and it has a greatest importance for patients receiving NACT in the preoperative period. Objective. Assessment of the immediate effectiveness of NACT and metastatic-free survival in patients with breast cancer depending on the presence of amplifications of regions of SG localization. in the primary breast tumor. Methods. Evaluation of the predictive and prognostic significance of the presence of amplifications of the SG loci 3q, 5p, 6p, 7q, 8q, 9p, 9q, 10p, 10q21.1, 12p, 13q, 16p, 18q, 19p in a breast tumor was carried out before treatment in 103 patients receiving NACT. Depending on the number of amplifications in the tumor, the patients were divided into two groups: with the presence of ≥2 amplifications in the tumor and with or without a single stemness gene amplification. SG amplification was determined using a high density CytoScanTM HD Array, Affymetrix (USA). Results. It has been established that SG amplifications in the primary tumor do not have predictive significance. The main result of the study was the identification of their prognostic significance. It was shown that the achievement of both complete and partial regression of neoplasm against NACT in breast cancer patients with ≥2 amplifications of any regions of SG localization in primary tumor tissue leads to a significant increase in metastatic-free survival (Log Rank [Mantel-Cox] p=0,025). At the same time, even a good response to NACT does not lead to an increase in the survival rate of patients with 0-1 amplification of SG. Conclusion. Thus, the results show that only patients with ≥2 SG amplifications have benefit from the treatment with NACT in terms of increasing survival, and these patients should receive NACT.

全文:

受限制的访问

作者简介

Polina Kazantseva

Tomsk National Research Medical Center of RAS

Email: polydoctor@yandex.ru
Scientific Research Institute of Oncology; PhD, Researcher at the Department of General Oncology, Scientific Research 5, Kooperativny Lane, Tomsk, 634050, Russian Federation

E. Slonimskaya

Tomsk National Research Medical Center of RAS; Siberian State Medical University

Scientific Research Institute of Oncology Tomsk, Russia

M. Tsyganov

Tomsk National Research Medical Center of RAS

Scientific Research Institute of Oncology Tomsk, Russia

M. Ibragimova

Tomsk National Research Medical Center of RAS; National Research Tomsk State University

Scientific Research Institute of Oncology Tomsk, Russia

A. Doroshenko

Tomsk National Research Medical Center of RAS

Scientific Research Institute of Oncology Tomsk, Russia

N. Tarabanovskaya

Tomsk National Research Medical Center of RAS

Scientific Research Institute of Oncology Tomsk, Russia

N. Litviakov

Tomsk National Research Medical Center of RAS; National Research Tomsk State University

Scientific Research Institute of Oncology Tomsk, Russia

参考

  1. Семиглазов В.Ф. Многоликая биология рака молочной железы: поиски адекватного лечения. Злокачественные опухоли. 2016;3(19):5-10.
  2. Schott A.F., Hayes D.F. Defining the benefits of neoadjuvant chemotherapy for breast cancer. Am Soc Clin Oncol. 2012:30(15):1747-49. doi: 10.1200/JCO.2011.41.3161.
  3. Proweii T.M., Pazdur R. Pathological complete response and accelerated drug approval in early breast cancer. N Engl J Med. 2012;366(26):2438-41. doi: 10.1056/NEJMp1205 737.
  4. Kaufmann M., von Minckwitz G., Mamounas E.P, et al. Recommendations from an international consensus conference on the current status and future of neoadjuvant systemic therapy in primary breast cancer. Ann Surg Oncol. 2012;19(5):1508-16. doi: 10.1245/s10434-011-2108-2.
  5. von Minckwitz G., Untch M., Loibi S. Update on neoadjuvant/preoperative therapy of breast cancer: experiences from the German Breast Group. Curr Opin Obstet Gynecol. 2013;25(1):66-73. Doi: 10.97/GCO.0b013e32835c0889.
  6. Ibragimova M., Tsyganov M., Litviakov N. Natural and chemotherapy-induced clonal evolution of tumors. Biochemistry (Moscow). 2017;82(4):413-25. doi: 10.1134/S0006297917040022.
  7. Oshima K., Khiabanian H., da Siiva-Aimeida A.C., et al. Mutational landscape, clonal evolution patterns, and role of RAS mutations in relapsed acute lymphoblastic leukemia. Proc Natl Acad Sci USA. 2016;113(40):11306-311
  8. Findlay J.M., Castro-Giner F., Makino S., et al. Differential clonal evolution in oesophageal cancers in response to neo-adjuvant chemotherapy. Nat Commun. 2016;7:11111. doi: 10.1038/ncomms11111.
  9. Roychoudhury S., Ghuwaiewaia S., Ghatak D., et al. MiR-146a-dependent regulation of CD24/ AKT/ß-catenin axis drives stem ceil phenotype in oral cancer. bioRxiv. 2018:429068. Doi: https://doi.org/10.1101/429068.
  10. Morel A.P, Lievre M., Thomas C., et al. Generation of breast cancer stem Cells through epithelial-mesenchymal transition. PLoS One. 2008;3(8):e2888. Doi: 10.13 71/journal. pone.0002888.
  11. Sato R., Semba T., Saya H., Arima Y Concise review: stem Cells and epithelial-mesenchymal transition in cancer: biological implications and therapeutic targets. Stem Cells. 2016;34(8):1997-2007. doi: 10.1002/stem.2406.
  12. Mani S.A., Guo W., Liao M.J., et al. The epithelialmesenchymal transition generates Cells with properties of stem Cells. Cell. 2008;133(4):704-15. doi: 10.1016/j.cell.2008.03.027.
  13. Ginestier C., Hur M.H., Charafe-Jauffret E., et al. ALDH1 is a marker of normal and malignant human mammary stem Cells and a predictor of poor clinical outcome. Cell stem cell. 2007;1(5):555-67. doi: 10.1016/j.stem.2007.08.014.
  14. Weiiner U., Schubert J., Burk U.C., et al. The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nature Ceil Biology. 2009;11(12):1487. doi: 10.1038/ncb1998.
  15. Suva M.L., Rheinbay E., Gillespie S.M., et al. Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like Cells. Ceil. 2014;157(3):580-94. doi: 10.1016/j.cell.2014.02.030.
  16. Zbinden M., Duquet A., Lorente-Trigos A., et al. NANOG regulates glioma stem Cells and is essential in vivo acting in a cross-functional network with GLI1 and p53. EMBO J. 2010;29(15):2659-74. doi: 10.1038/emboj.2010.137.
  17. Murakami S., Ninomiya W., Sakamoto E., et al. SRY and OCT4 Are Required for the Acquisition of Cancer Stem Cell-Like Properties and Are Potential Differentiation Therapy Targets. Stem Cells. 2015;33(9):2652- 63. doi: 10.1002/stem.2059.
  18. Song W.S., Yang Y.P, Huang C.S., et al. Sox2, a stemness gene, regulates tumor-initiating and drug-resistant properties in CD133-positive glioblastoma stem Cells. J Chinese Med Assoc. 2016;79(10):538-45. doi: 10.1016/j.jcma.2016.03.010.
  19. Chaffer C.L., Marjanovic N.D., Lee T., et al. Poised chromatin at the ZEB1 promoter enables breast cancer ceil plasticity and enhances tumorigenicity. Cell. 2013;154(1):61-74. doi: 10.1016/j.cell.2013.06.005.
  20. Shibue T., Weinberg R.A. EMT, CSCs, and drug resistance: the mechanistic link and clinical implications. Nature Rev Clin Oncol. 2017;14:611-29. doi: 10.1038/nrciinonc.2017.44.
  21. Cai H., Kumar N., Baudis M. arrayMap: A reference resource for genomic copy number imbalances in human malignancies. PLoS ONE. 2012;7(5):e36944. doi: 10.1371/journal.pone.0036944.
  22. Jönsson G., Staaf J., Vallon-Christersson J., et al. Research article Genomic subtypes of breast cancer identified by array-comparative genomic hybridization display distinct molecular and clinical characteristics. Breast Cancer Res. 2010;12(3):R42. doi: 10.1186/bcr2596.
  23. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663- 76.
  24. Zhang Y, Martens J.W., Jack X.Y., et al. Copy number alterations that predict metastatic capability of human breast cancer Cancer Res. 2009;69(9):3795-3801. doi: 10.1158/0008-5472.CAN-08-4596.
  25. Kim T.M., Xi R., Luquette L.J., et al. Functional genomic analysis of chromosomal aberrations in a compendium of 8000 cancer genomes. Genome Res. 2013;23(2):217-27. doi: 10.1101/gr.140301.112.
  26. Wikman H., Lamszus K., Detels N., et. al. Relevance of PTEN loss in brain metastasis formation in breast cancer patients. Breast Cancer Res. 2012;14(2):R49. Doi. 10.1186/bcr3150
  27. Pirozzi G., Tirino V., Camerlingo R., et al. Epithelial to mesenchymal transition by TGFß-1 induction increases stemness characteristics in primary non small cell lung cancer cell line. PLoS ONE. 2011;6(6):e21548. doi: 10.1371/journal. pone.0021548.
  28. Kumar S.M., Liu S., Lu H., et al. Acquired cancer stem cell phenotypes through Oct4-mediated dedifferentiation. Oncogene. 2012;31(47):489-911. doi: 10.1038/onc.2011.656.
  29. Lee G., Auffinger B., Guo D., et al. De-differentiation of glioma cells to glioma stem-like cells by therapeutic stress-induced HIF signaling in the recurrent GBM model. Molecular Cancer Therapeutics 2016:molcanther. 0675.2015. doi: 10.1158/1535-7163.MCT-15-0675.
  30. He K., Xu T., Goldkorn A. Cancer cells cyclically lose and regain drug-resistant highly tumorigenic features characteristic of a cancer stem-like phenotype. Mol Cancer Ther. 2011;10(6):938-48. doi: 10.1158/1535-7163.MCT-10-1120.

补充文件

附件文件
动作
1. JATS XML
下载
##common.cookie##