囊泡胺转运蛋白1激活非经典NF-κB信号通路对脑胶质瘤患者预后及治疗的影响  

Effects of activation of non-classical NF-κB signaling pathway by vesicle amine transport protein 1 on prognosis and treatment of glioma

作　　者：单侠 孙志延 王宽宇 保肇实[2] 杨沛[2] Shan Xia;Sun Zhiyan;Wang Kuanyu;Bao Zhaoshi;Yang Pei(Department of Radiotherapy,Beijing Tiantan Hospital,Capital Medical University,Beijing 100050,China;Department of Neurosurgery,Beijing Tiantan Hospital,Capital Medical University,Beijing 100050,China;Department of Stereotactic radiosurgery,Beijing Tiantan Hospital,Capital Medical University,Beijing 100050,China)

机构地区：[1]首都医科大学附属北京天坛医院放疗科,北京100050 [2]首都医科大学附属北京天坛医院神经外科,北京100050 [3]首都医科大学附属北京天坛医院立体定向放射外科,北京100050

出　　处：《中国微侵袭神经外科杂志》2025年第1期38-44,共7页Chinese Journal of Minimally Invasive Neurosurgery

基　　金：北京天坛医院苗圃计划项目(编号:MP23-6)。

摘　　要：目的 探究囊泡胺转运蛋白1(vesicle amine transport protein 1,VAT1)促进脑胶质瘤恶性表型的潜在机制。方法 纳入中国脑胶质瘤图谱(Chinese Glioma Genome Atlas,CGGA)数据库及美国癌症基因组图谱(The Cancer Genome Atlas Program,TCGA)数据库中全级别胶质瘤样本,结合VAT1表达情况,对临床信息及转录组数据进行分析,评估VAT1表达对于患者预后的影响。应用生物信息学分析技术,挖掘VAT1表达上调可能激活的信号通路。结果 本研究共纳入CGGA数据库226例和TCGA数据库651例全级别脑胶质瘤患者。生存分析显示:VAT1高表达患者总生存时间(overall survival,OS)明显缩短(P<0.001)。多因素Cox回归分析表明:VAT1表达是胶质瘤患者预后独立危险因素(HR=2.427,95%CI:1.451~4.061,P=0.001)。转录组数据分析显示:与VAT1表达正相关的基因功能涉及炎症及免疫反应、血管生成与缺氧反应,VAT1表达上调可能激活非经典NF-κB信号通路。对于治疗的影响分析提示:VAT1高表达患者存在放疗抵抗的情况。结论 脑胶质瘤患者VAT1高表达显著影响预后,导致治疗抵抗,抑制VAT1联合其他抗肿瘤治疗可能会加强抗肿瘤效应。Objective To explore the potential mechanism of vesicle amine transport protein 1(VAT1)in promoting the malignant phenotype of brain glioma.Methods All samples were downloaded from the Chinese Glioma Genome Atlas(CGGA)database and The Cancer Genome Atlas(TCGA)database.Combined with the expression of VAT1,clinical information and transcriptome data were analyzed to evaluate the effect of VAT1 expression on the prognosis of patients.Bioinformatics analysis was used to explore the possibly activated signal pathway with VAT1 up-regulation.Results A total of 226 patients with whole-grade glioma in CGGA database and 651 patients in TCGA database were included in this study.Survival analysis showed that the overall survival(OS)was significantly shortened in patients with high expression of VAT1(P<0.001).Multivariate Cox regression analysis showed that VAT1 expression was an independent prognostic factor in glioma patients(HR=2.427,95%CI:1.451-4.061,P=0.001).Transcriptome data analysis showed that the gene function positively related to VAT1 expression was involved in inflammation and immune response,angiogenesis and hypoxia response.The up-regulation of VAT1 expression may activate the non-classical NF-κB signaling pathway.Analysis of the impact on treatment suggests that the patient with high expression of VAT1 was resistant to radiotherapy.Conclusions The high expression of VAT1 in glioma patients significantly affects prognosis and leads to treatment resistance.Inhibition of VAT1 combined with other anti-tumor therapies may enhance anti-tumor effects.

关 键 词：神经胶质瘤 囊泡胺转运蛋白1 治疗抵抗 预后 

分 类 号：R739.41[医药卫生—肿瘤] R730.264[医药卫生—临床医学]