Abstract
Diffuse low-grade glioma (DLGG) is a well-differentiated, slow-growing tumour with an inherent tendency to progress to high-grade glioma. The potential roles of genetic alterations in DLGG development have not yet been fully delineated. Therefore, the current study performed an integrated gene expression meta-analysis of eight independent, publicly available microarray datasets including 291 DLGGs and 83 non-glioma (NG) samples to identify gene expression signatures associated with DLGG. Using INMEX, 708 differentially expressed genes (DEGs) (385 upregulated and 323 downregulated genes) were identified in DLGG compared to NG. Furthermore, 497 DEGs (222 upregulated and 275 downregulated genes) corresponding to two histological types were identified. Of these, high expression of HIP1R significantly correlated with increased overall survival, whereas high expression of TBXAS1 significantly correlated with decreased overall survival. Additionally, network-based meta-analysis identified FN1 and APP as the key hub genes in DLGG compared with NG. PTPN6 and CUL3 were the key hub genes identified in the astrocytoma relative to the oligodendroglioma. Further immunohistochemical validation revealed that MTHFD2 and SPARC were positively expressed in DLGG, whereas RBP4 was positively expressed in NG. These findings reveal potential molecular biomarkers for diagnosis and therapy in patients with DLGG and provide a rich and novel candidate reservoir for future studies.
Highlights
According to histological characteristics, gliomas can be classified into grades I–IV based on World Health Organization (WHO) criteria published in 2007 and 20161,2
The results showed that 1p/19q codeletion and isocitrate dehydrogenase 1 (IDH1) mutation are prognostic markers following the administration of radiotherapy or chemotherapy[8]
To identify possible differentially expressed genes (DEGs) between histological Diffuse low-grade glioma (DLGG) subtypes (A and OD, but not OA, which is not recognized as a separate tumour entity in the 2016 CNS tumour classification system2), an additional meta-analysis was performed to examine differences between A and OD samples
Summary
Gliomas can be classified into grades I–IV based on World Health Organization (WHO) criteria published in 2007 and 20161,2. Prior studies utilizing microarrays have identified numerous differentially expressed genes (DEGs), inconsistencies exist between studies due to variations in sample size and quality[9,10] To address this limitation, meta-analyses have been applied to synthesize the information available in publically available gene expression datasets to identify reliable molecular biomarkers of disease[11]. We used INMEX to perform meta-analyses of eight eligible microarray datasets to identify key regulators and potential diagnostic and therapy biomarkers associated with DLGG and its clinical subtypes. To the best of our knowledge, this study is the first to explore diagnostic and therapy biomarkers associated with DLGG and its histological subtypes by performing meta-analyses of gene expression datasets
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