Abstract
BackgroundWe aimed to explore the expression of forkhead box class O (FOXO) and relations between expressions of FOXOs and clinicopathological characteristics and prognosis of bladder cancer.MethodsWe enrolled a cohort of 276 patients with bladder cancer in our study. Expressions of FOXOs in bladder cancer tissue and adjacent tissue were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Correlations between expression of FOXOs and clinicopathological characteristics and prognosis were analyzed. The relationship between expression of FOXOs and survival time of patients with bladder cancer was analyzed by the Kaplan-Meier survival analysis and the Log-rank test; individual variables which may affect the prognosis of bladder cancer were detected by the Cox proportional hazard regression model.ResultsCompared with bladder cancer tissue, a higher expression of FOXOs was detected in paracancerous tissue. We found significant associations between histological grade and the expressions of FOXOs, clinical stage and the expressions of FOXOs, and lymph node metastasis and the expressions of FOXOs (all P < 0.05). When used for diagnosing bladder cancer, the mRNA expression of FOXO1/3/4 produced cut off values of 1.475, 1.305, and 1.295, respectively, exhibiting relatively high specificity and sensitivity. The Kaplan-Meier curves indicated that patients with a higher expression of FOXOs tended to have a longer overall survival than those with lower expression. The Cox regression analysis revealed that lymph node metastasis, high clinical stage, and low expression of FOXOs were independent risk factors for bladder cancer prognosis.ConclusionOur results indicate that the expression of FOXOs is closely correlated with clinicopathological characteristics and prognosis of bladder cancer.
Highlights
Arising from the epithelial layer of urinary bladder, bladder cancer is one of the most common malignant cancers in the world and its incidence has gradually increased, listed as the sixth most frequent form of cancer in 2013 [1]
Compared with bladder cancer tissue, a higher expression of forkhead box class O (FOXO) was detected in paracancerous tissue
We found significant associations between histological grade and the expressions of FOXOs, clinical stage and the expressions of FOXOs, and lymph node metastasis and the expressions of FOXOs
Summary
Arising from the epithelial layer of urinary bladder, bladder cancer is one of the most common malignant cancers in the world and its incidence has gradually increased, listed as the sixth most frequent form of cancer in 2013 [1]. FOXOs are closely related to the growth of cervical cancer cells through regulating the expression of certain proteins or genes [8]. Combination of FOXO1 and p53 can provide relevant prognostic information on progression and recurrence of bladder cancer [10]. The transcription factor FOXO3 is an effective tumor suppressor; dysregulation of FOXO3 is associated with cancer initiation and progression [11]. FOXO3 and FOXO4 may play an important role in cell apoptosis and the regulation of cell cycle in fetal membrane rupture [12]. FOXO4 is known as a tumor suppressor protein, which is closely related to the metastasis of cholangiocarcinoma [13]. We aimed to explore the expression of forkhead box class O (FOXO) and relations between expressions of FOXOs and clinicopathological characteristics and prognosis of bladder cancer
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