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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.

Gene expression meta-analysis in diffuse low-grade glioma and the corresponding histological subtypes