RUNX3 GENE METHYLATION AS A PROGNOSTIC FACTOR IN NON-MUSCLE-INVASIVE BLADDER CANCER
Abstract
The analysis of the RUNX3 gene methylation status was conducted in the prospective group of 262 bladder cancer patients. In comparison to normal urothelium, a high frequency (63 %) of RUNX3 promoter hypermethylation was observed in tumor tissues. А statistically significant association of RUNX3 epigenetic abnormalities with a more aggressive tumor phenotype – an advanced tumor stage and grade, as well as a large tumor size – was found. We have shown that RUNX3 hypermethylation is an independent risk factor for progression and cancer-specific survival in the group of patients with non-muscle invasive bladder cancer.
About the Authors
M. P. SMAL
Institute of Genetics and Cytology of the National Academy of Sciences of Belarus, Minsk
Belarus
Belarus
A. I. ROLEVICH
N. N. Alexandrov National Cancer Center of Belarus, Lesnoy
Belarus
Belarus
T. I. NABEBINA
N. N. Alexandrov National Cancer Center of Belarus, Lesnoy
Belarus
Belarus
S. A. KRASNY
N. N. Alexandrov National Cancer Center of Belarus, Lesnoy
Belarus
Belarus
R. I. GONCHAROVA
Institute of Genetics and Cytology of the National Academy of Sciences of Belarus, Minsk
Belarus
Belarus
References
1. Bladder cancer / F. de Braud [et al.] // Crit. Rev. Oncol. Hematol. – 2002. – Vol. 41, N 1. – P. 89–106.
2. Мутационный статус гена FGFR3 в проспективной когорте пациентов, страдающих раком мочевого пузыря / М. П. Смаль [и др.] // Докл. НАН Беларуси. – 2013. – Т. 57, № 1. – С. 96–101.
3. FGFR3 and TP53 mutations in a prospective cohort of Belarusian bladder cancer patients / M. P. Smal [et al.] // Exp. Oncol. – 2014. – Vol. 36, N 4. – P. 246–251.
4. Kandimalla, R. DNA methylation-based biomarkers in bladder cancer / R. Kandimalla, A. A. van Tilborg, E. C. Zwarthoff // Nat. Rev. Urol. – 2013. – Vol. 10, N 6. – P. 327–335.
5. RUNX3 inactivation by point mutations and aberrant DNA methylation in bladder tumors / W. J. Kim [et al.] // Cancer Res. – 2005. – Vol. 65, N 20. – P. 9347–9354.
6. Comprehensive genome methylation analysis in bladder cancer: identification and validation of novel methylated genes and application of these as urinary tumor markers / T. Reinert [et al.] // Clin. Cancer Res. – 2011. – Vol. 17, N 17. – P. 5582–5592.
7. Kim, Y. K. Epigenetic markers as promising prognosticators for bladder cancer / Y. K. Kim, W. J. Kim // Int. J. Urol. – 2009. – Vol. 16, N 1. – P. 17–22.
8. Levanon, D. Structure and regulated expression of mammalian RUNX genes / D. Levanon, Y. Groner // Oncogene. – 2004. – Vol. 23, N 24. – P. 4211–4219.
9. Runx3 inactivation is a crucial early event in the development of lung adenocarcinoma / Y. S. Lee [et al.] // Cancer Cell. – 2013. – Vol. 24, N 5. – P. 603–616.
10. Methylation of the RUNX3 promoter as a potential prognostic marker for bladder tumor / E. J. Kim [et al.] // J. Urol. – 2008. – Vol. 180, N 3. – P. 1141–1145.
11. RUNX3 methylation as a predictor for disease progression in patients with non-muscle-invasive bladder cancer / C. Yan [et al.] // J. Surg. Oncol. – 2012. – Vol. 105, N 4. – P. 425–430.
12. Prognostic significance of methylation profiles in urothelial carcinomas of the bladder / H. J. Park [et al.] // Korean J. Pathol. – 2010. – Vol. 44. – P. 623–630.
13. DNA methylation-associated inactivation of TGFbeta-related genes DRM/Gremlin, RUNX3, and HPP1 in human cancers / M. Suzuki [et al.] // Br. J. Cancer. – 2005. – Vol. 93, N 9. – P. 1029–1037.
14. RUNX3 methylation reveals that bladder tumors are older in patients with a history of smoking / E. M. Wolff [et al.] // Cancer Res. – 2008. – Vol. 68, N 15. – P. 6208–6214.
15. Methylation of tumor suppressor genes in a novel panel predicts clinical outcome in paraffin-embedded bladder tumors / R. García-Baquero [et al.] // Tumour Biol. – 2014. – Vol. 35, N 6. – P. 5777–5786.
Review
Views:
1047
Email this article 