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. SMALBelarus
A. I. ROLEVICH
Belarus
T. I. NABEBINA
Belarus
S. A. KRASNY
Belarus
R. I. GONCHAROVA
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.