Abstract
BackgroundGlioblastomas have a high degree of malignancy, high recurrence rate, high mortality rate, and low cure rate. Searching for new markers of glioblastomas is of great significance for improving the diagnosis, prognosis and treatment of glioma.MethodsUsing the GEO public database, we combined 34 glioma microarray datasets containing 1893 glioma samples and conducted genetic data mining through statistical analysis, bioclustering, and pathway analysis. The results were validated in TCGA, CGGA, and internal cohorts. We further selected a gene for subsequent experiments and conducted cell proliferation and cell cycle analyses to verify the biological function of this gene.ResultsEight glioblastoma-specific differentially expressed genes were screened using GEO. In the TCGA and CGGA cohorts, patients with high CBX3, BARD1, EGFR, or IFRD1 expression had significantly shorter survival but patients with high GUCY1A3 or MOBP expression had significantly longer survival than patients with lower expression of these genes. After reviewing the literature, we selected the CBX3 gene for further experiments. We confirmed that CBX3 was overexpressed in glioblastoma by immunohistochemical analysis of tissue microarrays and qPCR analysis of surgical specimens. The functional assay results showed that silencing CBX3 arrests the cell cycle in the G2/M phase, thereby weakening the cell proliferation ability.ConclusionsWe used a multidisciplinary approach to analyze glioblastoma samples in 34 microarray datasets, revealing novel diagnostic and prognostic biomarkers in patients with glioblastoma and providing a new direction for screening tumor markers.
Highlights
Glioblastomas have a high degree of malignancy, high recurrence rate, high mortality rate, and low cure rate
Some molecular biological markers are important for determining molecular subtypes, individualized treatment, and predicting prognosis, such as MGMT [7], epidermal growth factor receptor (EGFR) [8], IDH [9], 1p19q [10], ATRX [11], MGMT promoter methylation levels, 1p/19q-codeleted and IDH1 mutations can predict the prognosis of GBM, oligodendroglioma (OD) and low grade glioma [12]
In the The Cancer Genome Atlas (TCGA)-GBMLGG cohort, the results showed that patients with high chromobox homolog 3 (CBX3), BRCA1 associated RING domain 1 (BARD1), cathepsin S (CTSS), epidermal growth factor receptor (EGFR), interferon-related developmental regulator 1 (IFRD1), or signal transducer and activator of transcription 1 (STAT1) expression had significantly shorter survival but patients with high guanylate cyclase 1 soluble subunit alpha 3 (GUCY1A3) or myelin-associated oligodendrocytic basic protein (MOBP) expression had significantly longer survival than patients with lower expression of these genes
Summary
Glioblastomas have a high degree of malignancy, high recurrence rate, high mortality rate, and low cure rate. Some molecular biological markers are important for determining molecular subtypes, individualized treatment, and predicting prognosis, such as MGMT [7], EGFR [8], IDH [9], 1p19q [10], ATRX [11], MGMT promoter methylation levels, 1p/19q-codeleted and IDH1 mutations can predict the prognosis of GBM, oligodendroglioma (OD) and low grade glioma [12]. Emerging evidence supports mRNAs as potential biomarkers of glioblastomas, gene expression studies analyzed in isolation usually have inconsistent or discrepant results. Various factors, such as limited sample sizes, different profiling platforms, and diverse methods for data collection and analysis, lead to these discrepancies. The NCBI Gene Expression Omnibus (GEO) contains numerous human microarray datasets from various types of tissue biopsies, which can be used to discover disease-associated biomarkers. New approaches for the identification of novel biomarkers of gliomas are needed
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