Abstract
BackgroundGATA-5, a zinc-finger transcription factor and member of the GATA family proteins 1–6, is known to be involved in cellular differentiation. We recently found that tumor-specific hypermethylation of the GATA5 CpG island (CGI) occurs in renal cell carcinoma (RCC) and is associated with an adverse clinical outcome. In this study, we investigated whether epigenetic GATA5 alterations may result in changes in GATA5 mRNA expression levels and correlate with the observed prognostic impact of epigenetic changes in GATA5 in RCC.MethodsQuantitative real-time reverse-transcribed polymerase chain reaction was applied to measure relative GATA5 mRNA expression levels in 135 kidney tissue samples, including 77 clear cell RCC (ccRCC) tissues and 58 paired adjacent normal renal tissue samples. Relative GATA5 expression levels were determined using the ΔΔCt method and detection of three endogenous control genes then compared to previously measured values of relative methylation.ResultsThe mean relative GATA5 mRNA expression level exhibited an approximately 31-fold reduction in tumor specimens compared with corresponding normal tissues (p < 0.001, paired t-test). Decreased GATA5 mRNA expression was inversely correlated with increased GATA5 CGI methylation (p < 0.001) and was associated with shortened recurrence-free survival in ccRCC patients (p = 0.023, hazard ratio = 0.25).ConclusionGATA5 mRNA expression is decreased in ccRCC, likely due to gene silencing by methylation of the GATA5 CGI. Moreover, reduced GATA5 mRNA levels were associated with a poor clinical outcome, indicating a possible role of GATA5 for the development of aggressive ccRCC phenotypes.
Highlights
GATA-5, a zinc-finger transcription factor and member of the GATA family proteins 1–6, is known to be involved in cellular differentiation
GATA5 mRNA expression is decreased in Clear cell renal cell carcinomas (ccRCCs) The analyses of relative GATA5 mRNA expression levels revealed significantly decreased expression in tumor specimens (TU; mean lnRQ = −1.7; ±SD = 1.63) compared with the corresponding adjacent normal tissue (adN)
Loss of GATA5 mRNA expression is associated with decreased recurrence-free survival Cox regression survival analyses using a statistically calculated optimum cut off value for relative GATA5 mRNA expression showed that a lower expression status was associated with increased risk for shorter time to disease recurrence (p = 0.023, hazard ratio (HR) = 0.25, 95% confidence interval (CI): 0.07–0.82; Table 2)
Summary
GATA-5, a zinc-finger transcription factor and member of the GATA family proteins 1–6, is known to be involved in cellular differentiation. We recently found that tumor-specific hypermethylation of the GATA5 CpG island (CGI) occurs in renal cell carcinoma (RCC) and is associated with an adverse clinical outcome. As a member of the GATA family of transcription factors, GATA5 is known to be functionally involved in cellular lineage and cell differentiation during embryonic development of the heart, lung, urogenital tract, and gut epithelium [2]. Altered expression of GATA5 has been associated with intestinal epithelial cell differentiation [3]. In a recent study aimed at identifying new DNA methylation targets in ccRCC, we detected for the first time a tumor-specific hypermethylation of the GATA5 CpG island (CGI) in RCC [11]. Hypermethylation was associated with advanced disease and shortened recurrence-free survival (RFS) of patients
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
