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Background  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. 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.    Methods  Quantitative 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.    Results  The 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).    Conclusion   GATA5  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.

Decreased GATA5 mRNA expression associates with CpG island methylation and shortened recurrence-free survival in clear cell renal cell carcinoma