Association of gene expression with lymph node breast cancer metastasis

Cover Page


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

The most serious complication of breast cancer (BC), which affects life expectancy, is metastasis of the tumor. Metastasis is the cause of more than 80% of all breast cancer deaths. After surgical treatment and the use of adjuvant therapy, metastases occur in 8% – 15% of cases. This indicates the need to develop markers for the prognosis of metastasis and clarify its mechanisms for the creation of anti-metastatic therapeutic agents. In this paper, we studied the association of LOX and uPAR gene expression with breast cancer metastasis in the lymph nodes.

Gene expression was measured using real-time PCR in 40 paired samples (tumor-normal tissues). As a result of processing the measurements, the values of gene expression levels in the tumor tissue relative to normal were obtained.

It is shown that the LOX gene is expressed in the tumor both lower and higher relative to the norm, and uPAR is expressed in most cases higher. In metastatic tumors, the frequency of expression increases above the norm for both LOX and uPAR genes. The association of expression of these genes with lymphatic metastasis was found: p = 0.01 and p = 0.02, for the LOX and uPAR genes, respectively. The relative risk (RR) was for the LOX gene RR = 1.9, 95% CI 1.2 – 3, p = 0.005, for uPAR RR = 3.6, 95% CI 1.2 – 10.9, p = 0.03.

Thus, the data obtained contribute to understanding the mechanisms of metastasis and provide the basis for the development of new biomarkers. The LOX and uPAR genes may be candidates for predictive markers of breast cancer metastasis risk.

Full Text

Restricted Access

About the authors

K. A. Grishina

Research Centre for Medical Genetics (RCMG)

Author for correspondence.
Email: grstina@yandex.ru
ORCID iD: 0000-0002-0394-7801

researcher of the Laboratory of molecular genetics of complex inherited diseases

Russian Federation, Moscow

F. M. Kipkeeva

Research Centre for Medical Genetics (RCMG)

Email: grstina@yandex.ru
ORCID iD: 0000-0003-4778-9726
Russian Federation, Moscow

N. I. Pospekhova

Research Centre for Medical Genetics (RCMG)

Email: grstina@yandex.ru
ORCID iD: 0000-0001-5255-5065
Russian Federation, Moscow

V. A. Khaylenko

N.N. Blokhin National Medical Research Center of Oncology оf the Ministry of Health of the Russian Federation

Email: grstina@yandex.ru
ORCID iD: 0000-0002-9924-5854
Russian Federation, Moscow

A. V. Karpukhin

Research Centre for Medical Genetics (RCMG)

Email: grstina@yandex.ru
Russian Federation, Moscow

References

  1. Lord S.J, Marinovich M.L., Patterson J.A. et al. Incidence of metastatic breast cancer in an Australian population-based cohort of women with non-metastatic breast cancer at diagnosis. Med. J. Aust. 2012; 196: 688–92.
  2. van den Hurk C.J., Eckel R., van de Poll-Franse L.V. et al. Unfavourable pattern of metastases in M0 breast cancer patients during 1978-2008: a population-based analysis of the munich cancer registry. Breast Cancer Res. Treat. 2011; 128: 795–805.
  3. Hölzel D., Eckel R., Bauerfeind I. et al. Improved systemic treatment for early breast cancer improves cure rates, modifies metastatic pattern and shortens post-metastatic survival: 35-year results from the Munich Cancer Registry. J. Cancer Res. Clin. Oncol. 2017; 143: 1701–12.
  4. Lord S.J., Kiely B.E., Pearson S.-A. et al. Metastatic breast cancer incidence, site and survival in Australia, 2001–2016: a population-based health record linkage study protocol. BMJ Open. 2019; 9 (2): e026414. Published online 2019 Feb 1. doi: 10.1136/bmjopen-2018-026414.
  5. Wuest M., Kuchar M., Sharma S.K. et al. Targeting lysyl oxidase for molecular imaging in breast cancer. Breast Cancer Research. 2015; 17 (1): 107. doi: 10.1186/s13058-015-0609-9.
  6. Duffy M.J., O’Grady P., Devaney D. et al. Urokinase-plasminogen activator, a marker for aggressive breast carcinomas. Preliminary report. Cancer. 1988; 62 (3): 531˗3.
  7. Sun W.Y., Choi J., Cha Y.J., Koo J.S. Evaluation of the Expression of Amine Oxidase Proteins in Breast Cancer. Int. J. Mol. Sci. 2017; 18 (12): 2775. doi: 10.3390/ijms18122775.
  8. Xiao Q., Ge G. Lysyl oxidase, extracellular matrix remodeling and cancer metastasis. Cancer Microenviron. 2012; 5: 261–73.
  9. Grau-Bové X., Ruiz-Trillo I., Rodriguez-Pascuala F. Origin and evolution of lysyl oxidases. Sci Rep. 2015; 5: 10568. Published online 2015 May 29. doi: 10.1038/srep10568.
  10. Wuest M., Kuchar M., Sharma S.K. et al. Targeting lysyl oxidase for molecular imaging in breast cancer. Breast Cancer Res. 2015; 17: 107.
  11. Tong-Hong Wang T.-H., Shih-Min Hsia S.-M., Tzong-Ming ShiehT.-M. Lysyl Oxidase and the Tumor Microenvironment. Int. J. Mol. Sci. 2017; 18 (1): 62. Published online 2016 Dec 29. doi: 10.3390/ijms18010062.
  12. LeBeau A.M., Duriseti S., MurphyS.T. et al. Targeting uPAR with Antagonistic Recombinant Human Antibodies in Aggressive Breast Cancer. Cancer Res. 2013; 73 (7): 2070–81. doi: 10.1158/0008-5472.CAN-12-3526
  13. Jo M., Lester R.D., Montel V., Eastman B. et al. Reversibility of epithelial-mesenchymal transition (EMT) induced in breast cancer cells by activation of urokinase receptor-dependent cell signaling. J. Biol. Chem. 2009; 284: 22825–33.
  14. Huber C., Mall R., Braselmann H. et al. uPAR enhances malignant potential of triple-negative breast cancer by directly interacting with uPA and IGF1R. BMC Cancer. 2016; 16: 615. doi: 10.1186/s12885-016-2663-9.
  15. van Veen M. Matas-Rico E., van de Wetering K. et al. Negative regulation of urokinase receptor activity by a GPI-specific phospholipase C in breast cancer cells. eLife. 2017; 6:e23649. doi.org/10.7554/eLife.23649.

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2020 Eco-Vector



СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: ПИ № ФС 77 - 86496 от 11.12.2023 г
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: ЭЛ № ФС 77 - 80673 от 23.03.2021 г
.



This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies