Aberrant Expression of N-Methylpurine-DNA Glycosylase Influences Patient Survival in Malignant Gliomas

Ce Liu,Guoqiang Fu,Xinggang Mao,Yanyang Tu,Yongsheng Zhang,Liang Wang,Jun Yuan,Jianhai Zong,Shiming He

doi:10.1155/2012/760679

Abstract

Aim. To examine the expression of N-methylpurine-DNA glycosylase (MPG) gene and protein in glioma samples with different WHO grades and its association with patients' survival. Methods. Immunohistochemistry assay, quantitative real-time PCR and Western blot analysis were carried out to investigate the expression of MPG gene and protein in 128 glioma and 10 non-neoplastic brain tissues. Results. MPG gene expression level in glioma tissues was significantly higher than that in non-neoplastic brain tissues (P < 0.001). Immunohistochemistry also showed that MPG protein was over-expressed in glioma tissues, which was consistent with the resutls of Western blot analysis. Additionally, the expression levels of MPG gene and protein both increase from grade I to grade IV glioma according to the results of real-time PCR, immunohistochemistry and western blot analysis. Moreover, the survival rate of MPG-positive patients was significantly lower than that of MPG-negative patients (P < 0.001). We further confirmed that the over-expression of MPG was a significant and independent prognostic indicator in glioma by multivariate analysis (P < 0.001). Conclusions. Our data showed the over-expression of MPG gene and protein in human gliomas, and also suggested for the first time that MPG be an unfavorable independent prognostic indicator for glioma patients.

Highlights

Human gliomas represent 50% to 60% of all intracranial tumors [1]
There is an urgent need to further investigate the molecular mechanisms of glioma and to identify the effective prognostic indicators for survival prediction.The DNA-base excision repair (BER) pathway is responsible for the repair of exogenous and endogenous alkylating and oxidative DNA damage, which may lead to carcinogenesis, cell death, and aging if left unrepaired [7]
The gene expression of methylpurine-DNA glycosylase (MPG) normalized to β-actin in 20 glioma and 10 control brain tissues was detected by real-time polymerase chain reactions (PCRs)

Summary

Introduction

According to the World Health Organization (WHO) guidelines [2], gliomas are histologically classified into four grades: pilocytic astrocytoma (grade I), low-grade diffuse astrocytoma (grade II), anaplastic astrocytoma (grade III), and glioblastoma multiforme (GBM, grade IV). There have been several prognostic factors for glioma patients, such as age, preoperative duration of symptoms, Karnofsky performance status (KPS) score, histologic grade, tumor necrosis, surgical resection extent, use of postoperative radiation therapy, and, probably, adjuvant chemotherapy [5]. These clinical parameters cannot completely account for the observed variation in survival because of the heterogeneity of glioma patients [6]. We analyzed the relationship between MPG expression and the glioma stage as well as the survival of patients

Materials and Methods

Results

Discussion