Wang Chenglu, Yang Shuang, Jin Lu, Dai Guangcheng, Yao Qiu, Xiang Han, Zhang Yongsheng, Liu Xiaolong, Xue Boxin
Department of Urology, Second Affiliated Hospital of Soochow University, Suzhou 215004, People's Republic of China.
Department of Pathology, Second Affiliated Hospital of Soochow University, Suzhou 215004, People's Republic of China.
Onco Targets Ther. 2020 Jan 31;13:945-958. doi: 10.2147/OTT.S237099. eCollection 2020.
The purpose of the present study was to investigate the biological and clinical significance of GATA binding protein 3 (GATA3) in bladder cancer patients.
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.
The mRNA data from TCGA database and bladder cancer cell lines suggested that 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 ( 0.001 in TCGA; 0.004 in FFPE tissues), earlier clinical stage ( 0.001 in TCGA; 0.001 in FFPE) and lower grade tumor ( 0.057 in TCGA; 0.002 in FFPE). Kaplan-Meier analysis and multivariate Cox regression analysis indicated that age ( 0.001 in both cohort), clinical stage ( 0.028 in TCGA; 0.011 in FFPE), recurrence ( 0.001) and low GATA3 in TCGA cohort ( 0.035) but high GATA3 in FFPE cohort ( 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.
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.
本研究旨在探讨GATA结合蛋白3(GATA3)在膀胱癌患者中的生物学及临床意义。
为检测GATA3表达与膀胱癌之间的相关性,我们从癌症基因组图谱(TCGA)数据库下载了mRNA表达数据,并对福尔马林固定石蜡包埋(FFPE)样本组织进行免疫组化染色。然后,利用膀胱癌细胞系通过细胞凋亡、增殖及周期分析来研究GATA3的潜在功能。
来自TCGA数据库及膀胱癌细胞系的mRNA数据表明,与正常组织和细胞相比,mRNA表达显著更高。相反,蛋白质印迹分析显示,GATA3在膀胱癌中的表达明显低于正常尿路上皮细胞系。此外,我们发现GATA3的过表达与肿瘤亚型显著相关(TCGA中P = 0.001;FFPE组织中P = 0.004)、更早的临床分期(TCGA中P = 0.001;FFPE中P = 0.001)及更低分级的肿瘤(TCGA中P = 0.057;FFPE中P = 0.002)。Kaplan-Meier分析和多因素Cox回归分析表明,年龄(两个队列中P均为0.001)、临床分期(TCGA中P = 0.028;FFPE中P = 0.011)、复发(P = 0.001)以及TCGA队列中低水平的GATA3(P = 0.035)但FFPE队列中高水平的GATA3(P = 0.033)是患者总生存的独立危险因素。检测GATA3潜在功能的分析表明,该生物标志物可使T24细胞的细胞周期停滞在G2/M期和S期,并抑制膀胱癌细胞增殖。
总体而言,我们的研究结果表明GATA3是膀胱癌患者的重要预后生物标志物。然而,GATA3在膀胱癌中的作用机制值得进一步研究。