Wang Yang, Kang Xin-Li, Zeng Fan-Chang, Xu Cong-Jie, Zhou Jia-Quan, Luo Dong-Ni
Department of Urology, Hainan General Hospital, Haikou 570311, PR China.
Department of Urology, Hainan General Hospital, Haikou 570311, PR China.
Pathol Res Pract. 2017 Jul;213(7):766-772. doi: 10.1016/j.prp.2017.04.004. Epub 2017 Apr 20.
The study is performed to explore the correlations of forkhead box O3 (FoxO3) and forkhead box O4 (FoxO4) expressions with clinicopathological features and prognosis of bladder cancer.
Bladder cancer tissues and adjacent normal tissues from the recruited 222 patients were collected. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry were applied to determine the expressions of FoxO3 and FoxO4. Spearman correlation analysis was conducted to examine the correlation between the expressions of FoxO3 and FoxO4. All patients were followed up and overall survival (OS) and disease-free survival (DFS) were recorded. Kaplan-Meier survival curve was drawn to determine the associations of FoxO3 and FoxO4 expressions and postoperative survival. Cox proportional hazards model was conducted to analyze the risk factors for poor prognosis of bladder cancer.
The mRNA and expressions of FoxO3 and FoxO4 proteins in the bladder cancer tissues were lower than that in the adjacent normal tissues (both P<0.05). The positive rates of FoxO3 and FoxO4 were lower in the patients with lymph node metastasis than that in the patients without lymph node metastasis (P<0.05), and significantly lower in the patients with non-muscle invasive bladder cancer (T-T) than in those with non-muscle invasive bladder cancer (T-T) in TNM staging, and remarkably lower in the patients with high grade than in those with low grade in the histological type (P<0.05). Furthermore, the expressions of FoxO3 and FoxO4 were positively correlated in the bladder cancer tissues (P<0.05). Negative expressions of FoxO3 and FoxO4 and lymph node metastasis were the risk factors for the poor prognosis of bladder cancer.
The FoxO3 and FoxO4 expressions may potentially associate with the clinicopathological features and prognosis of bladder cancer.
本研究旨在探讨叉头框蛋白O3(FoxO3)和叉头框蛋白O4(FoxO4)表达与膀胱癌临床病理特征及预后的相关性。
收集222例入组患者的膀胱癌组织及癌旁正常组织。采用定量实时聚合酶链反应(qRT-PCR)、蛋白质免疫印迹法和免疫组织化学法检测FoxO3和FoxO4的表达。采用Spearman相关性分析检测FoxO3和FoxO4表达之间的相关性。对所有患者进行随访,记录总生存期(OS)和无病生存期(DFS)。绘制Kaplan-Meier生存曲线以确定FoxO3和FoxO4表达与术后生存的相关性。采用Cox比例风险模型分析膀胱癌预后不良的危险因素。
膀胱癌组织中FoxO3和FoxO4蛋白的mRNA及表达水平均低于癌旁正常组织(均P<0.05)。有淋巴结转移患者的FoxO3和FoxO4阳性率低于无淋巴结转移患者(P<0.05),TNM分期中Tis-T1期非肌层浸润性膀胱癌患者的FoxO3和FoxO4阳性率显著低于T2-T4期非肌层浸润性膀胱癌患者,组织学类型中高级别患者的FoxO3和FoxO4阳性率显著低于低级别患者(P<0.05)。此外,膀胱癌组织中FoxO3和FoxO4的表达呈正相关(P<0.05)。FoxO3和FoxO4的阴性表达及淋巴结转移是膀胱癌预后不良的危险因素。
FoxO3和FoxO4表达可能与膀胱癌的临床病理特征及预后相关。