Somatic CPEB4 and CPEB1 genes mutations spectrum on the prognostic predictive accuracy in patients with high-grade glioma and their clinical significance

https://doi.org/10.1016/j.jns.2016.02.032Get rights and content

Highlights

  • High expression of CPEB4 was correlated with shorter overall survival.

  • High protein expression of CPEB4 was related to advanced grade.

  • Low expression of CPEB1 was correlated with shorter overall survival.

  • CPEB1 mRNA levels were not correlated with clinicopathological features.

Abstract

Background

Glioblastoma (grade IV glioma/GBM) is characterized by extremely aggressive invasion and proliferative nature.

Objective

The main goal of this study was to evaluate the expression patterns of CPEB1 and CPEB4 in glioma patients.

Methods

41 paraffin-embedded tissue samples with glioma (WHO I–IV) were collected between January 2008 and December 2012 in Tehran, Iran. MRI of patients was done before and within 24 h after surgery and gliomas investigated using quantitative real-time PCR and immunohistochemistry. Kaplan-Meier survival and Cox regression were applied to assess the prognosis of patients.

Results

The mRNA level of CPEB4 was strongly increased in tumor tissues (0.67 ± 3.154 vs. 1.671 ± 0.51; P = 0.001). Furthermore, CPEB1 mRNA was significantly decreased in tumor tissues compared to normal tissues (2.852 ± 0.587 vs. 1.471 ± 0.862; P = 0.025). Our findings showed that CPEB4 levels was markedly increased in patients with advanced grade gliomas (P = 0.003). In addition, CPEB1 mRNA levels were not associated with clinicopathological features. Of the 41 cases, high CPEB4 expression was found in 29 patients (70.73%), while 12 cases (29.26%) showed weak expression levels, while the protein expression of CPEB4 were remarkably weak in normal tissues (P = 0.001). However, no correlation was found between expression levels of CPEB1 and clinicopathological characteristics. Kaplan-Meier survival and log-rank test indicated that high expression of CPEB4 was correlated with shorter overall survival (log-rank test P < 0.001). Furthermore, low expression of CPEB1 was linked to shorter overall survival (log-rank test P = 0.021). Multivariate Cox proportional hazards model showed that high CPEB1 (P = 0.027), low CPEB4 expressions (P = 0.021), and advanced tumor grade (P = 0.036) were independent predictor of overall survival.

Conclusion

Our data indicated expressions levels of CPEB4 and CPEB1 are correlated with overall survival in patients with glioma.

Introduction

Glioma is the most common primary brain tumor, accounting for 60–75% of glial tumors [1]. Glioblastoma (Grade IV glioma/GBM) is characterized by extremely aggressive invasion and proliferative nature, as well as it is associated with an extremely poor clinical outcome [2], [3], [4], [5]. The identification of valuable molecular markers can be beneficial for the prediction of patient prognosis and GBM tumor progression.

CPEB4 is a RNA binding protein that is a member of the CPEB family (CPEB1, CPEB2, CPEB3, and CPEB4)·CPEB4 has a crucial role in gene transcriptional regulation during tumor development. Previous studies indicated that increased CPEB4 expression is involved in tumor growth, migration, vascularization, invasion, and metastasis [6], [7], [8], [9], CPEB4 overexpression has been reported in some tumor types, including the glioblastoma cell line T98 (WHO grade IV), Glioma and pancreatic ductal carcinoma [6].

CPEB1 is indirectly associated with translational repression and activation via regulation of polyadenylation. CPEB1 has been indicated as a tumor suppressor in many kinds of tumors [10], [11]. In addition, it has been reported that elevated expression of CPEB1 act as inducer of differentiation during neural differentiation [12], [13]. The expression characteristics of CPEB4 in clinical samples of glioma patients needed further investigations. Therefore, we evaluated clinical significance of CPEB1 and CPEB4 in glioma patients with different grades.

Section snippets

Patients and Tissues.

41 Paraffin-embedded tissue samples with glioma (WHO I–IV) were collected between January 2008 and December 2012 in Tehran, Iran. MRI of patients was done before and within 24 h after surgery. The tumor specimens were confirmed according to the criteria of World Health Organization (WHO) Classification. Gliomas classified as WHO I, WHO II, WHO III, and WHO IV (glioblastoma). Normal brain tissues were collected during surgery for intractable epilepsy. The median follow-up for patients was 25 

MRNA levels

The mRNAs levels were evaluated in the glioma tissues and normal tissues using qRT-PCR assay. The mRNA level of CPEB4 was strongly increased in tumor tissues (0.67 ± 3.154 vs. 1.671 ± 0.51; P = 0.001), (Fig. 1). Furthermore, CPEB1 mRNA was significantly decreased in tumor tissues in comparison with normal tissues (2.852 ± 0.587 vs. 1.471 ± 0.862; P = 0.025), (Fig. 2). Our findings showed that CPEB4 levels was significantly higher in patients with advanced grade gliomas (P = 0.003). Moreover, CPEB1 mRNA

Discussion

CPEB is involved in important processes, such as cell senescence, synaptic plasticity, stem cell development, and cell differentiation.

Previous studies indicated that increased CPEB4 expression is involved in tumor growth, migration, vascularization, invasion, and metastasis [6], [7], [8], [9]. CPEB4 is related to a large number of CPE-containing mRNAs that are important targets for tumor specific translational regulation. In our study, the mRNA level of CPEB4 was strongly increased in tumor

Conclusions

In conclusion, our study indicated that CPEB4 expression is associated with advanced grade and shorter overall survival. In addition, low expression of CPEB1 was correlated with shorter overall survival.

Conflicts of interest

The authors declare that they have no conflict of interest.

Sources of funding

None.

Acknowledgements

None.

References (20)

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