Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
Front Immunol. 2022 Jun 14;13:915709. doi: 10.3389/fimmu.2022.915709. eCollection 2022.
Glioma, the most frequent malignant tumor of the neurological system, has a poor prognosis and treatment problems. Glioma's tumor microenvironment is also little known.
We downloaded glioma data from the TCGA database. The patients in the TCGA database were split into two groups, one for training and the other for validation. The ubiquitination genes were then evaluated in glioma using COX and Lasso regression to create a ubiquitination-related signature. We assessed the signature's predictive usefulness and role in the immune microenvironment after it was generated. Finally, experiment were utilized to check the expression and function of the signature's key gene, USP4.
This signature can be used to categorize glioma patients. Glioma patients can be separated into high-risk and low-risk groups in both the training and validation cohorts, with the high-risk group having a significantly worse prognosis (P<0.05). Following further investigation of the immune microenvironment, it was discovered that this risk grouping could serve as a guide for glioma immunotherapy. The activity, invasion and migration capacity, and colony formation ability of U87-MG and LN229 cell lines were drastically reduced after the important gene USP4 in signature was knocked down in cell tests. Overexpression of USP4 in the A172 cell line, on the other hand, greatly improved clonogenesis, activity, invasion and migration.
Our research established a foundation for understanding the role of ubiquitination genes in gliomas and identified USP4 as a possible glioma biomarker.
神经胶质瘤是最常见的神经系统恶性肿瘤,预后差,治疗困难。胶质瘤的肿瘤微环境也知之甚少。
我们从 TCGA 数据库中下载了胶质瘤数据。TCGA 数据库中的患者被分为两组,一组用于训练,另一组用于验证。然后使用 COX 和 Lasso 回归评估胶质瘤中的泛素化基因,以创建泛素化相关特征。生成后,我们评估了特征的预测有用性及其在免疫微环境中的作用。最后,利用实验检查了特征的关键基因 USP4 的表达和功能。
该特征可用于对胶质瘤患者进行分类。在训练和验证队列中,高风险组的患者可以分为高危组和低危组,高危组的预后明显较差(P<0.05)。进一步研究免疫微环境后发现,这种风险分组可以作为胶质瘤免疫治疗的指导。在细胞试验中,敲低特征中重要基因 USP4 后,U87-MG 和 LN229 细胞系的活性、侵袭和迁移能力以及集落形成能力大大降低。另一方面,A172 细胞系中 USP4 的过表达极大地提高了克隆形成、活性、侵袭和迁移。
我们的研究为理解泛素化基因在神经胶质瘤中的作用奠定了基础,并确定 USP4 为可能的神经胶质瘤生物标志物。