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Open Access Research article

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

Inga Peters1, Natalia Dubrowinskaja1, Michael Kogosov1, Mahmoud Abbas2, Jörg Hennenlotter3, Christoph von Klot1, Axel S Merseburger1, Arnulf Stenzl3, Ralph Scherer4, Markus A Kuczyk1 and Jürgen Serth1*

Author Affiliations

1 Department of Urology and Urologic Oncology, Hannover Medical School, Carl-Neuberg-Str.1, Hannover 30625, Germany

2 Department of Pathology, Hannover Medical School, Hannover, Germany

3 Department of Urology, Eberhard Karls University of Tuebingen, Tuebingen, Germany

4 Department of Biometry, Hannover Medical School, Hannover, Germany

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BMC Cancer 2014, 14:101  doi:10.1186/1471-2407-14-101

Published: 17 February 2014

Abstract

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.

Keywords:
GATA5; Renal cell carcinoma; mRNA; Prognosis; DNA methylation