Over-expression of Wild-type p53-induced phosphatase 1 confers poor prognosis of patients with gliomas

Dept. of Neurosurgery, The Second Hospital of Hebei Medical University, China.
Brain research (Impact Factor: 2.84). 03/2012; 1444:65-75. DOI: 10.1016/j.brainres.2011.12.052
Source: PubMed


Wild-type p53-induced phosphatase 1 (Wip1) is a member of the protein phosphatase 2C family, which is characterized by distinctive oncogenic properties. Overexpression of Wip1 is observed in certain types of human tumors that are associated with significantly poor prognosis. This study aimed to detect the expression of Wip1 in gliomas and to analyze its prognostic value in the patients. Wip1 mRNA and protein expression profiles in 81 gliomas and 15 normal brain tissues were detected using RT-PCR, Western blot and immunohistochemistry. The specimens were stained with proliferating cell nuclear antigen (PCNA) and p53 and evaluated using immunohistochemistry. Detailed clinical and demographic information of patients were retrospectively collected until 5years post-operation. Kaplan-Meier survival and Cox's regression analyses were performed to evaluate the prognosis of patients. Wip1-positive expression was observed in the majority of glioma tissues, whereas no Wip1 expression was detected in the normal brain tissues. Wip1-positive expression significantly correlated with glioma histological grade. The PCNA index was higher in the Wip1-positive group compared to that in the Wip1-negative group. A univariate analysis and log-rank test indicated that statistically significant association between Wip1 expression and the lower overall survival rate in the patients with glioma. A multivariate analysis also indicated a statistically significant association between increased Wip1 expression and lower overall survival rate. Our results suggest that Wip1 may be related to pathological diagnosis and prognosis evaluation for malignant gliomas.

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    • "On the other hand, tumors that retain wild-type p53 are likely to accumulate other genetic defects that would allow them to overcome the DDR barrier, providing a growth advantage in the presence of replicative stress. Importantly, amplification of the 17q23 locus carrying the PPM1D gene has been reported in various p53 wild-type tumors, pointing toward a role of Wip1 in cancer development, and Wip1 overexpression is associated with poor prognosis (Bulavin et al., 2002, 2004; Li et al., 2002; Saito-Ohara et al., 2003; Rauta et al., 2006; Castellino et al., 2008; Liang et al., 2012). The oncogenic behavior of Wip1 is further supported by mouse genetics showing that loss of Wip1 protects from cancer development (Bulavin et al., 2004; Nannenga et al., 2006). "
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