Abstract
BackgroundGliomas are the most common type of all central nervous system tumors. Almost all patients diagnosed with these tumors have a poor prognostic outcome. We aimed to identify novel glioma prognosis-associated candidate genes.MethodsWe applied WebArrayDB software to span platform integrate and analyze the microarray datasets. We focused on a subset of the significantly up-regulated genes, the minichromosome maintenance (MCM) family. We used frozen glioma samples to predict the relationship between the expression of MCMs and patients outcome by qPCR and western blot.ResultsWe found that MCMs expression was significantly up-regulated in glioma samples. MCM2-7 and MCM10 expressions were associated with WHO tumor grade. High MCM2 mRNA expression appeared to be strongly associated with poor overall survival in patients with high grade glioma. Furthermore, we report that MCM7 is strongly correlated with patient outcome in patients with WHO grade II-IV tumor. MCM3 expression was found to be up-regulated in glioma and correlated with overall survival in patients with WHO grade III tumor. MCM2, MCM3 and MCM7 expression levels were of greater prognostic relevance than histological diagnosis according to the current WHO classification system.ConclusionsHigh expression of MCM 2, MCM3 and MCM7 mRNA correlated with poor outcome and may be clinically useful molecular prognostic markers in glioma.
Highlights
Gliomas are the most common type of all central nervous system tumors
Our study indicates for the first time that high MCM2 mRNA expression appears to be strongly associated with poor overall survival in high grade glioma
We found a significant increase in MCM2 (3.5 fold), MCM3 (3.1 fold), MCM4 (4.3 fold), MCM5 (3.8 fold), MCM6 (3.5 fold), MCM7 (3.0 fold) and MCM10 (3.6 fold) expressions in tumor tissues compared to the normal brain controls
Summary
Gliomas are the most common type of all central nervous system tumors. Almost all patients diagnosed with these tumors have a poor prognostic outcome. Gliomas represent a group of low grade and high grade brain tumors that originate from glial cells. The median survival for patients with anaplastic astrocytoma (WHO grade III) and glioblastoma (WHO grade IV) is less than threes years and less than one year, respectively [2]. All types of cancer as well as glioma constitute a major public health problem that presents several challenges to researchers such as identification of biomarkers for improved and early diagnosis, classification of tumors, and the definition of targets for more effective treatment. Large-scale association genome-wide surveys have been used to identify new biomarkers that have been developed as diagnostic and prognostic tools
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