Validation of the functions and prognostic values of synapse-associated proteins in lower-grade glioma.
Validation of the functions and prognostic values of synapse-associated proteins in lower-grade glioma.
复制标题
低级别胶质瘤中突触相关蛋白的功能和预后价值的验证
DOI：
10.1042/bsr20210391
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发表时间：
2021-05-28
影响因子：
4
通讯作者：
Zhou D
中科院分区：
文献类型：
--
作者：
Lin H;Yang Y;Hou C;Huang Y;Zhou L;Zheng J;Lv G;Mao R;Chen S;Xu P;Zhou Y;Wang P;Zhou D
摘要突触和突触相关蛋白（SAP）在各种神经退行性疾病和脑肿瘤中起着重要作用。然而，在低级别胶质瘤（LGG），SAP尚未系统地探讨。本研究旨在探讨SAPs在LGG中的表达及其临床病理意义，为胶质瘤的治疗提供新的思路。在本研究中，我们整合了一个SAP列表，涵盖了231个具有突触发生活性和突触后形成的蛋白质。LGG RNA-seq数据从GEO、TCGA和CGGA数据库下载。PPI关键模块中与预后相关的SAP被认为是枢纽SAP。Western blot、定量逆转录PCR（qRT-PCR）和HPA数据库中的免疫组化结果用于验证hub SAP的表达。与正常脑组织相比，LGG组织中有68个SAP表达上调，44个SAP表达下调。功能富集分析揭示了差异表达的SAP在LGG突触组织和突触能受体通路中的功能。生存分析显示GRIK 2、GABRD、GRID 2和ARC四种SAP与LGG患者的预后相关。有趣的是，我们发现GABRD在LGG患者癫痫发作中上调，表明SAP可能与胶质瘤患者癫痫发作的发病机制有关。四个SAP签名被揭示为胶质瘤的独立预后因素。我们的研究提出了一种新的策略来评估LGG的预后风险，基于SAP的表达。
Abstract 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.
影响因子：
2.4
作者：
Zeng W;Gillis T;Hakky M;Djoussé L;Myers RH;MacDonald ME;Gusella JF
通讯作者：
Gusella JF