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Differential Expression of Hypoxia-Related Genes in Primary Brain Tumors and Correlation With Clinicopathologic Data Publisher Pubmed



Bayat S1 ; Mamivand A1 ; Khoshnevisan A2 ; Maghrouni A1 ; Shabani S1 ; Raouf MT2 ; Yaseri M3 ; Saffar H4 ; Tabrizi M1
Authors
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Authors Affiliations
  1. 1. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Neurosurgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

Source: World Neurosurgery Published:2021


Abstract

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 investigations conducted include receiver operating characteristic 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) 1α expression in glioma samples compared with meningioma 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 P values 0.0005, <0.0001, and <0.0001 for GPRC5A, HIF1α, 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, HIF1α, 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. © 2021 Elsevier Inc.