Biological and Clinical Significance of GATA3 Detected from TCGA Database and FFPE Sample in Bladder Cancer Patients

摘要

Purpose: The purpose of the present study was to investigate the biological and clinical significance of GATA binding protein 3 (GATA3) in bladder cancer patients. Patients and Methods: For the detection of the correlation between GATA3 expression and bladder cancer, we downloaded the mRNA expression data from the Cancer Genome Atlas (TCGA) database and conducted immunohistochemistry staining on formalin-fixed paraffin-embedded (FFPE) sample tissues. Then, bladder cancer cell lines were utilized to investigate the potential functions of GATA3 by cell apoptosis, proliferation and cycle assays. Results: The mRNA data from TCGA database and bladder cancer cell lines suggested that GATA3 mRNA expression was significantly higher compared with normal tissues and cells. Conversely, the Western blot assay revealed that the expression of GATA3 was significantly lower in bladder cancer than normal urothelial cell line. Additionally, we found that over-expression of GATA3 was significantly associated with tumor subtype ( P = 0.001 in TCGA; P = 0.004 in FFPE tissues), earlier clinical stage ( P 0.001 in TCGA; P 0.001 in FFPE) and lower grade tumor ( P = 0.057 in TCGA; P = 0.002 in FFPE). Kaplan-Meier analysis and multivariate Cox regression analysis indicated that age ( P 0.001 in both cohort), clinical stage ( P = 0.028 in TCGA; P = 0.011 in FFPE), recurrence ( P 0.001) and low GATA3 in TCGA cohort ( P = 0.035) but high GATA3 in FFPE cohort ( P = 0.033) were independent risk factors for overall survival in patients. The assay to detect potential functions of GATA3 indicated that this biomarker could arrest the cell cycle of G2/M and S phase in T24 cells, and inhibit bladder cancer cells proliferation. Conclusion: Collectively, our findings identified that GATA3 served as an important prognosis biomarker for bladder cancer patients. However, the mechanism of GATA3 in bladder cancer deserves further studies.