title: Decreased GATA5 mRNA expression associates with CpG island methylation and shortened recurrence-free survival in clear cell renal cell carcinoma.
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).
  
  
  CONCLUSIONS
  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.
authors.forename: Inga
authors.initials: I
authors.lastname: Peters
authors.forename: Natalia
authors.initials: N
authors.lastname: Dubrowinskaja
authors.forename: Michael
authors.initials: M
authors.lastname: Kogosov
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Abbas
authors.forename: Jörg
authors.initials: J
authors.lastname: Hennenlotter
authors.forename: Christoph
authors.initials: C
authors.lastname: von Klot
authors.forename: Axel S
authors.initials: AS
authors.lastname: Merseburger
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
authors.forename: Ralph
authors.initials: R
authors.lastname: Scherer
authors.forename: Markus A
authors.initials: MA
authors.lastname: Kuczyk
authors.affiliation: Department of Urology and Urologic Oncology, Hannover Medical School, Carl-Neuberg-Str,1, Hannover 30625, Germany. serth.juergen@mh-hannover.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Serth
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000401:mortality; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D050992:GATA5 Transcription Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D015996:Survival Rate / Q000639:trends
chemical_list: D014408:Biomarkers, Tumor; D050992:GATA5 Transcription Factor; C494755:GATA5 protein, human; D012333:RNA, Messenger