title: Decreased mRNA expression of GATA1 and GATA2 is associated with tumor aggressiveness and poor outcome in clear cell renal cell carcinoma.
abstract: GATA-binding proteins 1 (GATA1) and 2 (GATA2) are zinc-finger transcription factors and belong to the GATA family proteins 1-6. GATA1 interacts with the TP53 tumor suppressor gene, and both GATAs have been shown to be involved in cell growth, apoptosis, and tumorigenesis of several solid tumors. GATA1 and GATA2 expression alterations are associated with poor survival and adverse clinicopathology in prostate and colorectal cancer, while the significance and prognostic value in clear cell renal cell carcinoma (ccRCC) has not been investigated as yet. We investigated relative messenger RNA (mRNA) expression levels of GATA1 and GATA2 in 77 ccRCC and 58 paired adjacent noncancerous renal tissues by quantitative real-time reverse-transcribed PCR. Relative mRNA expression levels were determined using the ΔΔCt method. GATA1 and GATA2 expression levels were significantly decreased in tumor tissues compared with normal tissues (p < 0.001, paired t test). In univariate logistic regression analysis, decreased GATA1 and GATA2 expression levels were associated with advanced tumor disease (p = 0.005 and 0.008), positive distant metastasis (p = 0.03 and 0.001), and lymph node metastasis status (p = 0.011 and 0.038). Reduced expression levels of GATA1 and GATA2 were associated with an increased risk of disease recurrence (p = 0.005 and 0.006; hazard ratio = 0.05 and 0.21). Pairwise bivariate analysis after adjusting for clinicopathological parameters revealed relative mRNA expression of GATA1, but not GATA2, as an independent candidate prognosticator for ccRCC. Our results support that GATA1 and GATA2 are involved in ccRCC tumor biology possibly affecting tumor development and aggressiveness.
authors.affiliation: Department of Urology and Urologic Oncology, Hannover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany, peters.inga@mh-hannover.de.
authors.forename: Inga
authors.initials: I
authors.lastname: Peters
authors.forename: Natalia
authors.initials: N
authors.lastname: Dubrowinskaja
authors.forename: Hossein
authors.initials: H
authors.lastname: Tezval
authors.forename: Mario W
authors.initials: MW
authors.lastname: Kramer
authors.forename: Christoph A
authors.initials: CA
authors.lastname: von Klot
authors.forename: Jörg
authors.initials: J
authors.lastname: Hennenlotter
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.forename: Jürgen
authors.initials: J
authors.lastname: Serth
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D003430:Cross-Sectional Studies; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D050982:GATA1 Transcription Factor / Q000235:genetics*; D050989:GATA2 Transcription Factor / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D012333:RNA, Messenger