GATA5 CpG island hypermethylation is an independent predictor for poor clinical outcome in renal cell carcinoma

Peters,Inga; Gebauer,Kai; Dubrowinskaja,Natalia; Atschekzei,Faranaz; Kramer,Mario W.; Hennenlotter,Joerg; Tezval,Hossein; Abbas,Mahmoud; Scherer,Ralph; Merseburger,Axel S.; Stenzl,Arnulf; Kuczyk,Markus A.; Serth,Juergen

doi:10.3892/or.2014.3030

GATA5 CpG island hypermethylation is an independent predictor for poor clinical outcome in renal cell carcinoma

Authors:
- Inga Peters
- Kai Gebauer
- Natalia Dubrowinskaja
- Faranaz Atschekzei
- Mario W. Kramer
- Joerg Hennenlotter
- Hossein Tezval
- Mahmoud Abbas
- Ralph Scherer
- Axel S. Merseburger
- Arnulf Stenzl
- Markus A. Kuczyk
- Juergen Serth
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Affiliations: Department of Urology and Urologic Oncology, Hannover Medical School, D-30625 Hannover, Germany, Department of Urology, Eberhard-Karls University, D-72076 Tuebingen, Germany, Department of Pathology, Hannover Medical School, D-30625 Hannover, Germany, Department of Biometry, Hannover Medical School, D-30625 Hannover, Germany
Published online on: February 18, 2014 https://doi.org/10.3892/or.2014.3030
Pages: 1523-1530
Copyright: © Peters et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Transcriptional inactivation and CpG island (CGI) methylation of GATA transcription factor family members GATA3 and GATA5 have been reported for a few types of human cancer. Whether high-density CGI methylation of GATA3 or GATA5 is associated with the clinical course of patients with renal cell cancer (RCC) has not been clarified. Quantitative methylation-specific PCR assays were carried out to analyze 25 tumor cell lines including 6 RCC lines and 119 RCC and 87 adjacent normal tissues for the presence of densely methylated sequences. Methylation values were statistically compared with clinicopathological and recurrence-free survival (RFS) data for patients. Comparison of GATA3 and GATA5 methylation in different tumor cell lines revealed a marker-specific methylation characteristic with high and frequent signals for both methylation marks in RCC lines. GATA3 and GATA5 CGI relative methylation levels were found to be strongly associated with the state of metastasis (P=0.003 and P<0.001, respectively) and advanced disease (P=0.024 and P<0.001, respectively). Moreover, an independent decrease in RFS in Cox proportional hazard analysis was found for tumors exhibiting high GATA5 methylation (P<0.001, hazard ratio, 19.3; 95% confidence interval, 4.58-81.6). Epigenetic alterations in GATA family members may be associated with aggressive tumor phenotypes in RCC, and in the case of GATA5, may serve as a new independent molecular marker for aggressiveness and disease progression.

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