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存活素、β-连环蛋白和p53在尿路上皮癌中的表达及其预后意义

Prognostic significance of survivin, β-catenin and p53 expression in urothelial carcinoma.

作者信息

Senol Serkan, Yildirim Asif, Ceyran Bahar, Uruc Fatih, Zemheri Ebru, Ozkanli Seyma, Akalin Ibrahim, Ulus Ismail, Caskurlu Turhan, Aydin Abdullah

机构信息

Medeniyet Univercity Goztepe Research and Training Hospital Istanbul TURKEY.

出版信息

Bosn J Basic Med Sci. 2015 Aug 19;15(4):7-14. doi: 10.17305/bjbms.2015.556.

Abstract

Survivin, β-catenin, and p53 are well-known cell-cycle and apoptosis regulators of tumorigenesis. Urothelial carcinomas (UCs) are the most common of the human cancers. Compared to superficial tumors (Ta, CIS, or T1), invasive UCs are important with regard to recurrence, progression, and mortality. Therefore, we examined whether survivin, β-catenin, and p53 could be used as the biomarkers for the early prediction of the invasiveness of UCs and the overall survival of the patients. We investigated the prognostic expressions of those biomarkers in UC (n=147) and in non-muscle invasive UC (NMI-UC) (n=113), using tissue microarray and immunohistochemistry. Spearman's correlation analysis and multivariate Cox regression analyses were used for statistical interpretation. High expressions of β-catenin, survivin, and p53 were associated with a high T stage, recurrence, progression, mortality, low recurrence-free survival, low progression-free survival and low overall survival (p <0.01). Similar findings were achieved for recurrence and progression in the NMI-UC group, except for mortality. Moreover, a positive correlation was shown between p53 and β-catenin and between p53 and survivin (r=0.221, p <0.01; r=0.236, p <0.01, respectively). Survivin, p53, and β-catenin overexpression, as prognostic markers, might suggest that the UCs are biologically aggressive with the poor prognosis. Thus, dysregulation of those these cell-cycle and apoptosis regulators in bladder carcinoma could be used as a molecular marker to determine the best treatment strategy and could contribute to the development of targeted therapies.

摘要

生存素、β-连环蛋白和p53是肿瘤发生过程中众所周知的细胞周期和凋亡调节因子。尿路上皮癌(UCs)是人类最常见的癌症。与浅表性肿瘤(Ta、CIS或T1)相比,浸润性UCs在复发、进展和死亡率方面更为重要。因此,我们研究了生存素、β-连环蛋白和p53是否可作为早期预测UCs浸润性和患者总生存期的生物标志物。我们使用组织芯片和免疫组化方法,研究了这些生物标志物在UC(n = 147)和非肌层浸润性UC(NMI-UC)(n = 113)中的预后表达。采用Spearman相关性分析和多变量Cox回归分析进行统计学解释。β-连环蛋白、生存素和p53的高表达与高T分期、复发、进展、死亡率、低无复发生存率、低无进展生存率和低总生存率相关(p <0.01)。在NMI-UC组中,除死亡率外,复发和进展方面也有类似发现。此外,p53与β-连环蛋白之间以及p53与生存素之间呈正相关(r分别为0.221,p <0.01;r为0.236,p <0.01)。生存素、p53和β-连环蛋白的过表达作为预后标志物,可能提示UCs具有生物学侵袭性且预后不良。因此,膀胱癌中这些细胞周期和凋亡调节因子的失调可作为确定最佳治疗策略的分子标志物,并有助于靶向治疗的发展。

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