Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Key Laboratory of Immune Microenvironment and Disease, Ministry of Education, Key Laboratory of Cellular and Molecular Immunology in Tianjin, Excellent Talent Project, Tianjin Medical University, Tianjin, China.
Cancer Med. 2021 Apr;10(8):2826-2839. doi: 10.1002/cam4.3829. Epub 2021 Mar 12.
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.
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.
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.
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.
新兴的癌基因与临床胶质瘤的复杂亚型和发病机制有关。在此，我们首次通过生物信息学分析和细胞实验全面探讨生长停滞特异性双家族基因（GAS2、GAS2L1、GAS2L2、GAS2L3）与胶质瘤之间的潜在相关性。
基于 TCGA（癌症基因组图谱）、CGGA（中国脑胶质瘤基因组图谱）和 Oncomine 数据库中的可用数据集，我们进行了一系列分析，如基因表达、生存预后、DNA 甲基化、免疫浸润和伙伴富集。我们还利用两种神经胶质瘤细胞系进行了集落形成和划痕愈合实验。
与正常脑组织相比，GAS2L3 基因在胶质瘤组织中高表达（p<0.05）。我们进一步观察到在我们的 Cox 比例风险模型中，高表达的 GAS2L3 与脑低级别胶质瘤（LGG）病例的不良临床预后之间的关系（风险比[HR]=0.1715，p<0.001）。此外，GAS2L3 的 DNA 低甲基化状态与 LGG 组织中 GAS2L3 的高表达和原发性神经胶质瘤病例的不良临床预后相关（p<0.05）。我们还发现，GAS2L3 的高表达与免疫细胞，尤其是 T 细胞的浸润水平相关（p<0.0001）。GAS2L3 相关基因和相互作用伙伴的功能富集分析进一步表明，GAS2L3 可能通过影响一系列生物学行为，如细胞分裂、细胞骨架结合和细胞黏附，参与胶质瘤的发生。此外，我们的细胞实验数据表明，高表达的 GAS2L3 基因有助于增强神经胶质瘤细胞的增殖和迁移。
本研究首次分析了 GAS2 家族基因，特别是 GAS2L3，在胶质瘤临床预后和可能的功能机制中的潜在作用，为 GAS2L3 与 LGG 之间的关系提供了新的见解。
