Hu Li, Cheng Xingbo, Binder Zev, Han Zhibin, Yin Yibo, O'Rourke Donald M, Wang Sida, Feng Yumeng, Weng Changjiang, Wu Anhua, Lin Zhiguo
Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Neurosurgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States.
Front Oncol. 2021 May 27;11:640910. doi: 10.3389/fonc.2021.640910. eCollection 2021.
Glioblastoma is the most common and lethal brain cancer globally. Clinically, this cancer has heterogenous molecular and clinical characteristics. Studies have shown that UBE2S is highly expressed in many cancers. But its expression profile in glioma, and the correlation with clinical outcomes is unknown. RNA sequencing data of glioma samples was downloaded from the Chinese Glioma Genome Atlas and The Cancer Genome Atlas. A total of 114 cases of glioma tissue samples (WHO grades II-IV) were used to conduct protein expression assays. The molecular and biological characteristics of UBE2S, and its prognostic value were analyzed. The results showed that high UBE2S expression was associated with a higher grade of glioma and PTEN mutations. In addition, UBE2S affected the degree of malignancy of glioma and the development of chemo-radiotherapy resistance. It was also found to be an independent predictor of worse survival of LGG patients. Furthermore, we identified five UBE2S ubiquitination sites and found that UBE2S was associated with Akt phosphorylation in malignant glioblastoma. The results also revealed that UBE2S expression was negatively correlated with 1p19q loss and IDH1 mutation; positively correlated with epidermal growth factor receptor amplification and PTEN mutation. This study demonstrates that UBE2S expression strongly correlates with glioma malignancy and resistance to chemo-radiotherapy. It is also a crucial biomarker of poor prognosis.
胶质母细胞瘤是全球最常见且致命的脑癌。临床上,这种癌症具有异质性的分子和临床特征。研究表明,UBE2S在许多癌症中高表达。但其在胶质瘤中的表达谱以及与临床结果的相关性尚不清楚。从中国胶质瘤基因组图谱和癌症基因组图谱下载胶质瘤样本的RNA测序数据。共使用114例胶质瘤组织样本(WHO二级至四级)进行蛋白质表达检测。分析了UBE2S的分子和生物学特征及其预后价值。结果表明,UBE2S高表达与较高等级的胶质瘤和PTEN突变相关。此外,UBE2S影响胶质瘤的恶性程度和放化疗耐药性的发展。还发现它是低级别胶质瘤患者生存较差的独立预测因子。此外,我们鉴定了五个UBE2S泛素化位点,并发现UBE2S与恶性胶质母细胞瘤中的Akt磷酸化相关。结果还显示,UBE2S表达与1p19q缺失和IDH1突变呈负相关;与表皮生长因子受体扩增和PTEN突变呈正相关。这项研究表明,UBE2S表达与胶质瘤恶性程度和放化疗耐药性密切相关。它也是预后不良的关键生物标志物。