Kao Ying, Tsai Wen-Chiuan, Chen Ssu-Han, Hsu Shao-Yuan, Huang Li-Chun, Chang Chih-Ju, Huang Shih-Ming, Hueng Dueng-Yuan
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.
Division of Neurosurgery, Department of Surgery, Taipei City Hospital Zhongxing Branch, Taipei, Taiwan, ROC.
Sci Rep. 2021 Sep 17;11(1):18541. doi: 10.1038/s41598-021-97119-4.
Glioblastomas are the most common type of adult primary brain neoplasms. Clinically, it is helpful to identify biomarkers to predict the survival of patients with gliomas due to its poor outcome. Shugoshin 2 (SGO2) is critical in cell division and cell cycle progression in eukaryotes. However, the association of SGO2 with pathological grading and survival in patients with gliomas remains unclear. We analyzed the association between SGO2 expression and clinical outcomes from Gene Expression Omnibus (GEO) dataset profiles, The Cancer Genome Atlas (TCGA), and Chinese Glioma Genome Atlas (CGGA). SGO2 mRNA and protein expression in normal brain tissue and glioma cell lines were investigated via quantitative RT-PCR, Western blot, and IHC staining. The roles of SGO2 in proliferation, migration, and apoptosis of GBM cells were studied with wound-healing assay, BrdU assay, cell cycle analysis, and JC-1 assay. The protein-protein interaction (PPI) was analyzed via Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). SGO2 mRNA expression predicted higher grade gliomas than non-tumor brain tissues. Kaplan-Meier survival analysis showed that patients with high-grade gliomas with a higher SGO2 expression had worse survival outcomes. SGO2 mRNA and protein expression were upper regulated in gliomas than in normal brain tissue. Inhibition of SGO2 suppressed cell proliferation and migration. Also, PPI result showed SGO2 to be a potential hub protein, which was related to the expression of AURKB and FOXM1. SGO2 expression positively correlates with WHO pathological grading and patient survival, suggesting that SGO2 is a biomarker that is predictive of disease progression in patients with gliomas.
胶质母细胞瘤是成人原发性脑肿瘤中最常见的类型。临床上,由于胶质瘤患者预后较差,识别生物标志物以预测其生存情况很有帮助。Shugoshin 2(SGO2)在真核生物的细胞分裂和细胞周期进程中至关重要。然而,SGO2与胶质瘤患者病理分级及生存的关联仍不清楚。我们分析了来自基因表达综合数据库(GEO)、癌症基因组图谱(TCGA)和中国胶质瘤基因组图谱(CGGA)的数据集概况中SGO2表达与临床结果之间的关联。通过定量逆转录聚合酶链反应、蛋白质印迹法和免疫组化染色研究了正常脑组织和胶质瘤细胞系中SGO2 mRNA和蛋白质的表达。采用划痕实验、BrdU实验、细胞周期分析和JC-1实验研究了SGO2在胶质母细胞瘤细胞增殖、迁移和凋亡中的作用。通过检索相互作用基因/蛋白质的搜索工具(STRING)分析了蛋白质-蛋白质相互作用(PPI)。SGO2 mRNA表达预测高级别胶质瘤高于非肿瘤脑组织。Kaplan-Meier生存分析表明,SGO2表达较高的高级别胶质瘤患者生存结果较差。与正常脑组织相比,胶质瘤中SGO2 mRNA和蛋白质表达上调。抑制SGO2可抑制细胞增殖和迁移。此外,PPI结果显示SGO2是一种潜在的枢纽蛋白,与极光激酶B(AURKB)和叉头框蛋白M1(FOXM1)的表达有关。SGO2表达与世界卫生组织病理分级及患者生存呈正相关,提示SGO2是预测胶质瘤患者疾病进展的生物标志物。