DNA methylation is the most common and well-characterized epigenetic change in human cancer. Recently, the association between GATA-binding protein 5 (GATA5) methylation and carcinogenesis of various types of tumors was investigated. The aim of the present study was to evaluate the effect of GATA5 methylation status on clinicopathological features and prognosis in primary non-muscle invasive bladder cancer (NMIBC) patients with a long-term follow-up period. The GATA5 methylation status was determined for 171 human bladder specimens (eight normal controls [NCs] and 163 primary NMIBC patients) using quantitative pyrosequencing analysis. The primary NMIBC tissues were obtained from patients who underwent transurethral resection (TUR) for histologically diagnosed transitional cell carcinomas between 1995 and 2012 at Chungbuk National University Hospital. GATA5 methylation was significantly higher in NMIBC patients than in NCs and was significantly associated with higher grade and more advanced stage of cancer. Kaplan-Meier estimates showed significant differences in tumor recurrence and progression according to GATA5 methylation status (each p<0.05). Our results show that increased methylation of GATA5 was significantly associated with not only aggressive characteristics but also poor prognosis in primary NMIBC patients. Alteration of GATA5 methylation might be used as a biomarker for prognosis of NMIBC patients. However, prospective and functional investigations are necessary to clarify the role of GATA5 methylation in future clinical management of patients with NMIBC.

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• Hyung-Yoon Yoon(R&D center, Advanced Technology,Cheongju 28413, Korea)
• Sung Pil Seo(Department of Urology, College of Medicine, Chungbuk National University, Cheongju 28644, Korea)
• Sang Keun Lee(Department of Urology, College of Medicine, Chungbuk National University, Cheongju 28644, Korea)
• Ho Won Kang(Department of Urology, College of Medicine, Chungbuk National University, Cheongju 28644, Korea)
• Won Tae Kim(Department of Urology, College of Medicine, Chungbuk National University, Cheongju 28644, Korea)
• Dong Hee Ryu(Department of Surgery, College of Medicine, Chungbuk National University, Cheongju 28644, Korea)
• Seok-Joong Yun(Department of Urology, College of Medicine, Chungbuk National University, Cheongju 28644, Korea)
• Sang-Cheol Lee(Department of Urology, College of Medicine, Chungbuk National University, Cheongju 28644, Korea)
• Wun-Jae Kim(Department of Urology, College of Medicine, Chungbuk National University, Cheongju 28644, Korea)
• Yong-June Kim(Department of Urology, College of Medicine, Chungbuk National University, Cheongju 28644, Korea) Corresponding Author