Integrative analysis regarding the correlation between GAS2 family genes and human glioma prognosis. (12th March 2021)

• Record Type: Journal Article
• Authors: Zhao, Chunyan; Zhang, Nan; Cui, Xiaoteng; Zhang, Xinxin; Ren, Yuanyuan; Su, Chao; He, Jinyan; Zhang, Wei; Sun, Xiaoming; Yang, Jie; Gao, Xingjie
• Is Part Of: Cancer medicine. Volume 10:Number 8(2021)
• Page Start: 2826
• Page End: 2839
• Publication Date: 2021-03-12
• Subjects: GAS2 -- GAS2L1 -- GAS2L2 -- GAS2L3 -- glioma; 616.994005
• DOI: 10.1002/cam4.3829
• Languages: English
• ISSNs: 2045-7634

Abstract

Abstract: Background: Emerging oncogenes were reportedly linked to the complicated subtypes and pathogenesis of clinical gliomas. Herein, we first comprehensively explored the potential correlation between growth‐arrest‐specific two family genes ( GAS2, GAS2L1, GAS2L2, GAS2L3 ) and gliomas by bioinformatics analysis and cellular experiments. Methods: Based on the available datasets of TCGA (The Cancer Genome Atlas), CGGA (Chinese Glioma Genome Atlas), and Oncomine databases, we performed a series of analyses, such as gene expression, survival prognosis, DNA methylation, immune infiltration, and partner enrichment. We also utilized two glioma cell lines to conduct the colony formation and wound‐healing assay. Results: GAS2L3 gene was highly expressed in glioma tissues compared to normal brain tissues ( p < 0.05). We further observed the relationship between the high expressed GAS2L3 and poor clinical prognosis of brain low‐grade glioma (LGG) cases in our Cox proportional hazard model (hazard ratio [HR] = 0.1715, p < 0.001). Moreover, DNA hypomethylation status of GAS2L3 was correlated with the high expression of GAS2L3 in LGG tissues and the poor clinical prognosis of primary glioma cases ( p < 0.05). We also found that the high expression of GAS2L3 was associated with the infiltration level of immune cells, especially the T cells ( p < 0.0001). Functional enrichment analysis of GAS2L3 ‐correlated genes and interaction partners further indicated that GAS2L3 might take part in the occurrence of glioma by influencing a series of biological behaviors, such as cell division, cytoskeleton binding, and cell adhesion. Additionally, our cellular experiment data suggested that a highly expressed GAS2L3 gene contributes to the enhanced proliferation and migration of glioma cells. Conclusion: This study first analyzed the potential role of GAS2 family genes, especially GAS2L3, in the clinical prognosis and possible functional mechanisms of glioma, which gives a novel insight into the relationship between GAS2L3 and LGG. Abstract : Compared with GAS2, GAS2L1, and GAS2L2, there is a stronger correlation between GAS2L3 gene expression and glioma prognosis. DNA hypomethylation of GAS2L3 may contribute to the high expression level of GAS2L3 and the poor clinical prognosis of glioma. GAS2L3 gene is capable of influencing the proliferation and migration ability of glioma cells and may be linked to a series of immune cell infiltration or cell division‐associated events in the etiology and biology of glioma.