Purpose: p21 protein is an inhibitor of cyclin-dependent kinases, which may be able to arrest the cell cycle at the G1 phase by inhibiting DNA replication through the interaction with proliferating cell nuclear antigen. From experimental studies, p21 has been considered a tumor suppressor gene. Herein, the effects of p21 on the development, stage, grade, recurrence, progression and patient's survival in human bladder cancers were evaluated. Materials and Methods: The mRNA expression levels of p21 were examined in 149 tumor specimens obtained from patients with primary bladder cancer and in 18 normal bladder mucosae using real-time polymerase chain reaction (PCR). Results: p21 was significantly expressed in human bladder tumor tissues at high levels (7.11+/-0.69pg/ml), but was not expressed in the normal bladder mucosae. Compared with invasive bladder cancer (5.03+/-0.95), the p21 expression levels were significantly enhanced in superficial bladder cancer (7.96+/-0.88pg/ml) (p=0.0250); whereas, the grade was not related to the expression of p21. The levels of p21 expression were enhanced in non-recurred (9.33+/-1.38) and non-progressed (8.13+/-0.86) compared with recurred (6.03+/-0.75) and progressed (3.67+/-0.52) patients (each p<0.05). The level of p21 expression was significantly correlated with the disease free survival in patients the bladder cancers. Conclusions: The enhanced expression of p21 is strongly associated with the development of bladder cancer. Moreover, increased expressions of p21 are also positively associated with the low rate of recurrence and progression of bladder cancer. Conversely, an enhanced expression of p21 provides a survival benefit for patients with bladder cancer. These results suggest that p21 might be useful as a marker in assessing tumor diagnosis, recurrence, progression and the survival in human bladder cancer patients.
Cell Cycle ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclin-Dependent Kinases ; Diagnosis ; Disease-Free Survival ; DNA Replication ; G1 Phase ; Genes, Tumor Suppressor ; Humans ; Mucous Membrane ; Polymerase Chain Reaction ; Proliferating Cell Nuclear Antigen ; Real-Time Polymerase Chain Reaction ; Recurrence ; RNA, Messenger ; Urinary Bladder Neoplasms* ; Urinary Bladder*