Correlations of Foxo3 and Foxo4 expressions with clinicopathological features and prognosis of bladder cancer

Abstract

Objective: 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.

Methods: 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.

Results: 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_is-T₁) than in those with non-muscle invasive bladder cancer (T₂-T₃) 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.

Conclusions: The FoxO3 and FoxO4 expressions may potentially associate with the clinicopathological features and prognosis of bladder cancer.

Keywords: Bladder cancer; Clinicopathological features; Forkhead box O3; Forkhead box O4; Prognosis.