Yang Feng-Qiang, Huang Jian-Hua, Liu Min, Yang Feng-Ping, Li Wei, Wang Guang-Chun, Che Jian-Ping, Zheng Jun-Hua
Department of Urology, Shanghai Tenth People's Hospital, Tongji University Shanghai, 200072, China.
Department of Urology, Shanghai Tenth People's Hospital, Tongji University Shanghai, 200072, China ; Department of Medicine, People's Hospital in Xinyuan County Xinjiang Province, Xinjiang, 835800, China.
Int J Clin Exp Pathol. 2013 Dec 15;7(1):340-7. eCollection 2014.
Argonaute 2 proteins (Ago2) have been demonstrated to be widely expressed and involved in post-transcriptional gene silencing and play key roles in carcinogenesis. However, its expression profile and prognostic value in urothelial carcinoma of the bladder (UCB) have not been investigated.
Real-time quantitative PCR (qRT-PCR) and Western blot were used to explore Ago2 expression in UCBs and normal bladder tissues. Moreover immunohistochemistry (ICH) was used to detect the expression of Ago2 in UCBs. Spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data.
Up-regulated expression of Ago2 mRNA and protein was observed in the majority of UCBs by qRT-PCR and Western blot when compared with their paired normal bladder tissues. Clinic pathological analysis was showed a significant correlation existed between the higher expression of Ago2 protein with the Histological grade, lymph node metastasis and Distant metastasis (P<0.05); Survival analysis by Kaplan-Meier survival curve and log-rank test demonstrated that elevated Ago2 expression in cancer tissue predicted poorer overall survival (OS) compared with group in lower expression (62.2% VS 86.3%, P<0.05). Notably, multivariate analyses by Cox's proportional hazard model revealed that expression of Ago2 was an independent prognostic factor in UCB.
These results suggest that the aberrant expression of Ago2 in human UCB is possibly involved with tumorigenesis and development, and the Ago2 protein could act as a potential biomarker for prognosis assessment of bladder cancer. Further studies on the cellular functions of Ago2 need to address these issues.
已证明Argonaute 2蛋白(Ago2)广泛表达并参与转录后基因沉默,在致癌过程中起关键作用。然而,其在膀胱尿路上皮癌(UCB)中的表达谱和预后价值尚未得到研究。
采用实时定量PCR(qRT-PCR)和蛋白质印迹法探讨Ago2在UCB组织和正常膀胱组织中的表达。此外,采用免疫组织化学(ICH)检测Ago2在UCB中的表达。使用Spearman等级相关性分析、Kaplan-Meier曲线和Cox比例风险回归模型分析数据。
与配对的正常膀胱组织相比,通过qRT-PCR和蛋白质印迹法在大多数UCB组织中观察到Ago2 mRNA和蛋白表达上调。临床病理分析显示,Ago2蛋白的高表达与组织学分级、淋巴结转移和远处转移之间存在显著相关性(P<0.05);通过Kaplan-Meier生存曲线和对数秩检验进行的生存分析表明,癌组织中Ago2表达升高预示总体生存率(OS)较表达较低组更差(62.2%对86.3%,P<0.05)。值得注意的是,Cox比例风险模型的多因素分析显示,Ago2的表达是UCB的独立预后因素。
这些结果表明,Ago2在人UCB中的异常表达可能与肿瘤发生和发展有关,Ago2蛋白可作为膀胱癌预后评估的潜在生物标志物。需要对Ago2的细胞功能进行进一步研究以解决这些问题。