Differential Expression of Hypoxia-Related Genes in Primary Brain Tumors and Correlation with Clinicopathologic Data

OBJECTIVE: Meningiomas and gliomas are common benign and malignant primary brain tumors, respectively. One of the most prominent features of aggressive malignancies contributing to their progression is their ability to cope with hypoxia. Therefore, glioma tumors are expected to better cope with adverse hypoxic conditions and, consequently, display significantly different expression levels of hypoxia-adaptive genes. METHODS: Thirty-three glioma (17 glioblastoma multiforme [GBM], 16 low-grade glioma [LGG]) and 32 meningioma samples were investigated for expression of hypoxia adaptation- related genes by real-time polymerase chain reaction. The same investigation was carried out for GBM, the most malignant form of glioma, versus LGG. The findings were further checked by bioinformatics analysis of expression levels using RNA-seq data. Additional in-vestigations conducted include receiver operating charac-teristic curve analysis to assess the power for each gene in differential diagnosis of glioma from meningioma. RESULTS: A greater level of hypoxia-inducible factor (HIF) 1a expression in glioma samples compared with me- -ingioma and greater expression levels of Yes-associated protein (YAP) 1 and G-protein-coupled receptor class C group 5 member A (GPRC5A) in meningioma were observed, with Pvalues 0.0005, <0.0001, and <0.0001 for GPRC5A, HIF1a, and YAP1, respectively. Comparison of GBM with LGG also revealed GPRC5A to have significantly greater expression in GBM with P [ 0.0381. The calculated area under the curve was 0.7536, 0.8438, and 0.8272 for GPRC5A, HIF1a, and YAP1, respectively, which represented acceptable power for these genes in differential diagnosis of glioma tumor types from meningioma and tumor subtypes GBM from LGG under study. CONCLUSIONS: These results imply that these genes can possibly be implicated in brain tumor hypoxia-adaptation response with tumor-specific roles and patterns of expression.