TY - JOUR
T1 - GATA5 CpG island hypermethylation is an independent predictor for poor clinical outcome in renal cell carcinoma
AU - Peters, Inga
AU - Gebauer, Kai
AU - Dubrowinskaja, Natalia
AU - Atschekzei, Faranaz
AU - Kramer, Mario W.
AU - Hennenlotter, Joerg
AU - Tezval, Hossein
AU - Abbas, Mahmoud
AU - Scherer, Ralph
AU - Merseburger, Axel S.
AU - Stenzl, Arnulf
AU - Kuczyk, Markus A.
AU - Serth, Juergen
N1 - Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2014/4
Y1 - 2014/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84908144618&partnerID=8YFLogxK
U2 - 10.3892/or.2014.3030
DO - 10.3892/or.2014.3030
M3 - Journal articles
C2 - 24549248
AN - SCOPUS:84908144618
SN - 1021-335X
VL - 31
SP - 1523
EP - 1530
JO - Oncology Reports
JF - Oncology Reports
IS - 4
ER -
