Abstract
Background Glioma is the most common malignant tumor of the brain in adult patients. The standardized treatment protocol is based on surgical therapy, supplemented with radiotherapy and chemotherapy. However, the prognosis is still unsatisfied. Chemoresistance is one of the most important reason for the poor prognosis of glioma patients. It has confirmed that glioma stem cell (GSC) is one of the reasons for chemoresistance. Methods In this study, three datasets (GSE23806, COSMIC, and TCGA) were used to perform the analysis to search for the key genes related to GSC, temozolomide (TMZ) resistance, and prognosis. The key gene for further research was selected by reviewing the previous studies. The selected gene investigated the relation between expression levels and clinical characteristics in both TCGA and CGGA dataset. The bioinformatics analysis was performed by Gene Ontology (GO) analysis. The survival analysis was performed by Kaplan–Meier survival analysis. Results AE binding protein 1 (AEBP1) was selected for further analysis. AEBP1 was overexpressed in GSCs and TMZ resistance cells. In both TCGA and CGGA dataset, the results showed that the expression level of AEBP1 was increased in glioblastoma (GBM) samples, IDH wild-type samples, and MGMT promoter unmethylated samples. Meanwhile, AEBP1 expression was positively related to several GSC markers. GO analysis showed that AEBP1 was related to immune response, cell adhesion, apoptotic process, inflammatory response, positive regulation of cell proliferation, angiogenesis, response to drug, and response to hypoxia. The survival analysis showed that the overexpressed level of AEBP1 was correlated with short survival time in both glioma and GBM patients. Conclusion In summary, AEBP1 was related with GSC-induced TMZ resistance. Our study showed that AEBP1 might be an oncogene and a new effective therapeutic target for the treatment of glioma.
Highlights
Glioma is the most prevalent type of primary brain tumor in adults which is devastated to patients [1]
The other four genes were EFEMP2, GPX2, NUDT9, and PTPRN2. As it was showed in the figures, the RNA expression level of AE binding protein 1 (AEBP1) was higher in glioma stem cell (GSC) and TMZ resistance cell lines than the non-GSCs and TMZ-sensitive cell lines (Figures 1(b) and 1(c))
The expression level of AEBP1 during different grades of glioma was analyzed in two datasets, and the results showed that it was higher in GBM patients than that in lower-grade glioma patients (Figures 2(a) and 2(b))
Summary
Glioma is the most common malignant tumor of the brain in adult patients. The standardized treatment protocol is based on surgical therapy, supplemented with radiotherapy and chemotherapy. Three datasets (GSE23806, COSMIC, and TCGA) were used to perform the analysis to search for the key genes related to GSC, temozolomide (TMZ) resistance, and prognosis. The selected gene investigated the relation between expression levels and clinical characteristics in both TCGA and CGGA dataset. AEBP1 was overexpressed in GSCs and TMZ resistance cells. In both TCGA and CGGA dataset, the results showed that the expression level of AEBP1 was increased in glioblastoma (GBM) samples, IDH wild-type samples, and MGMT promoter unmethylated samples. The survival analysis showed that the overexpressed level of AEBP1 was correlated with short survival time in both glioma and GBM patients. Our study showed that AEBP1 might be an oncogene and a new effective therapeutic target for the treatment of glioma
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