Department of Neurosurgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Shantou University Medical College, Shantou, China.
Biosci Rep. 2021 May 28;41(5). doi: 10.1042/BSR20210391.
Synapse and synapse-associated proteins (SAPs) play critical roles in various neurodegeneration diseases and brain tumors. However, in lower-grade gliomas (LGG), SAPs have not been explored systematically. Herein, we are going to explore SAPs expression profile and its clinicopathological significance in LGG which can offer new insights to glioma therapy. In the present study, we integrate a list of SAPs that covered 231 proteins with synaptogenesis activity and post synapse formation. The LGG RNA-seq data were downloaded from GEO, TCGA and CGGA database. The prognosis associated SAPs in key modules of PPI (protein-protein interaction networks) was regarded as hub SAPs. Western blot, quantitative reverse transcription PCR (qRT-PCR) and immunochemistry results from HPA database were used to verify the expression of hub SAPs. There were 68 up-regulated SAPs and 44 down-regulated SAPs in LGG tissue compared with normal brain tissue. Data from function enrichment analysis revealed functions of differentially expressed SAPs in synapse organization and glutamatergic receptor pathway in LGGs. Survival analysis revealed that four SAPs, GRIK2, GABRD, GRID2 and ARC were correlate with the prognosis of LGG patients. Interestingly, we found that GABRD were up-regulated in LGG patients with seizures, indicating that SAPs may link to the pathogenesis of seizures in glioma patients. The four-SAPs signature was revealed as an independent prognostic factor in gliomas. Our study presented a novel strategy to assess the prognostic risks of LGGs, based on the expression of SAPs.
突触和突触相关蛋白（SAPs）在各种神经退行性疾病和脑肿瘤中发挥着关键作用。然而，在低级别胶质瘤（LGG）中，SAPs 尚未得到系统研究。在此，我们将探讨 SAPs 在 LGG 中的表达谱及其与临床病理特征的关系，以期为胶质瘤的治疗提供新的思路。在本研究中，我们整合了一份涵盖 231 种具有突触发生活性和突触后形成的 SAPs 的列表。从 GEO、TCGA 和 CGGA 数据库中下载 LGG 的 RNA-seq 数据。将 PPI（蛋白质-蛋白质相互作用网络）关键模块中与预后相关的 SAPs 视为枢纽 SAPs。Western blot、定量逆转录 PCR（qRT-PCR）和 HPA 数据库的免疫化学结果用于验证枢纽 SAPs 的表达。与正常脑组织相比，LGG 组织中上调的 SAPs 有 68 个，下调的 SAPs 有 44 个。功能富集分析的数据显示，差异表达的 SAPs 在 LGG 中参与突触组织和谷氨酸能受体通路的功能。生存分析显示，GRIK2、GABRD、GRID2 和 ARC 这四个 SAPs 与 LGG 患者的预后相关。有趣的是，我们发现 GABRD 在伴有癫痫发作的 LGG 患者中上调，这表明 SAPs 可能与胶质瘤患者癫痫的发病机制有关。四-SAPs 标志物被证实是胶质瘤的独立预后因素。本研究提出了一种基于 SAPs 表达评估 LGG 预后风险的新策略。
