Expression of CPEB4 in Human Glioma and Its Correlations With Prognosis

Abstract

CPEB4 plays an important role in cancer progression. However, the clinicopathological significance of CPEB4 expression to glioma and its expression levels in glioma tissues and cell lines are unknown. The present study investigated the potential prognostic value of CPEB4 for human glioma.Immunohistochemistry (IHC) was performed to examine the dynamics of CPEB4 expression in glioma and nonneoplastic brain tissues, and the expression of CPEB4 in cell lines and freshly prepared tissue samples was measured using Western blotting and real-time PCR.CPEB4 was highly expressed at the mRNA and protein levels in 4 glioma cell lines and in 4 freshly prepared glioma tissues. Immunohistochemical analysis demonstrated that CPEB4 expression in glioma tissue was higher than that in corresponding nonneoplastic brain tissue (P < 0.01). This high expression level was further increased in high-grade gliomas, and the CPEB4 expression level correlated with the WHO classification (r = 0.774, P < 0.01). Moreover, the overall survival of glioma patients displaying high CPEB4 protein expression (P < 0.01) was clearly lower than that of those displaying low CPEB4 expression, and the high CPEB4 expression indicated a poorer survival in high-grade glioma patients (P < 0.01).Our study suggests that CPEB4 is significantly expressed in human glioma and that the upregulation of CPEB4 protein is significantly associated with advanced WHO grade. CPEB4 may serve as a highly sensitive prognostic indicator for glioma patients.

FIGURE 1

The expression of CPEB4 in glioma samples based on real-time PCR and Western blotting. From left to right: the human glioblastoma cell line SKMG-4, the human glioma cell line SHG-44, the human glioblastoma cell line U87, the human glioblastoma cell line T98, the human lung carcinoma cell lines A549 (positive control), freshly prepared sample B430 (WHO III), freshly prepared sample B099 (WHO I), freshly prepared sample B315 (WHO IV), and freshly prepared sample B958 (normal brain tissue). (A) Expression of the CPEB4 protein in glioma cell lines and freshly prepared tissue samples. (B) Fold change in CPEB4 protein expression in glioma cell lines and freshly prepared tissue samples. (C) Fold change in CPEB4 mRNA expression in glioma cell lines and freshly prepared tissue samples.

FIGURE 2

Representative sections of CPEB4 immunoreactivity in glioma and nonneoplastic brain tissues (left, ×20; right, ×400). The CPEB4 protein was primarily expressed in the cytoplasm, as demonstrated by brownish yellow staining.

FIGURE 3

The box plots demonstrate the range of CPEB4 expression (based on the immunohistochemical score) for each group (normal brain tissues, N = 41; low-grade glioma tissues, N = 92; and high-grade glioma tissues, N = 136).

FIGURE 4

Kaplan–Meier survival curves of glioma patients. (A) The OS of all glioma patients with CPEB4 protein expression: high versus low. (B) The OS of high CPEB4 protein expression and low CPEB4 protein expression in high-grade glioma patients. (C) The OS of high CPEB4 protein expression and low CPEB4 protein expression in low-grade glioma patients. (D) The OS of glioma patients with high WHO grade (III–IV) was significantly lower than that of glioma patients with low WHO grade (I–II).