脑胶质瘤PSMA5的表达、功能及临床意义  

Expression,function and clinical significance of PSMA5 in glioma

作　　者：李南丁 贾博 王赞 李成才 王冀伟 桂宇凡 刘伟[1] LI Nanding;JIA Bo;WANG Zan;LI Chengcai;WANG Jiwei;GUI Yufan;LIU Wei(Department of Neurosurgery,The First Hospital of Hebei Medical University,Shijiazhuang 050000,China)

机构地区：[1]河北医科大学第一医院神经外科,石家庄050000

出　　处：《临床神经外科杂志》2024年第6期629-635,共7页Journal of Clinical Neurosurgery

基　　金：河北省自然科学基金基础研究项目(H2023206403);河北省卫生健康委医学科学研究课题计划项目(20221385)。

摘　　要：目的 研究蛋白酶体Alpha-5亚单位(PSMA5)在脑胶质瘤中的表达情况、功能及临床意义。方法 利用获取自癌症基因组图谱(TCGA)和中国脑胶质瘤基因组图谱(CGGA)的胶质瘤样本信息,通过生物信息学方法分析PSMA5的表达情况。利用DESeq2 R程序包筛选出差异表达基因(DEGs),并通过基因本体论(GO)和基因集富集分析(GSEA)进行功能富集分析。利用单因素和多因素Cox回归分析和Kaplan-Meier法评估PSMA5对患者预后的影响。利用SiRNA敲低PSMA5的表达以探究其对胶质瘤细胞生长的影响。结果 PSMA5在胶质瘤患者中呈高表达(P<0.05),且在高级别胶质瘤及异柠檬酸脱氢酶1(IDH1)野生型胶质瘤患者中有更高的表达水平(P<0.05)。GO和GSEA分析结果显示,PSMA5与免疫反应、有丝分裂等密切相关。Cox分析的结果表明,PSMA5的高表达是胶质瘤的一个显著独立预后因素(CGGA:P<0.01,TCGA:P=0.032);Kaplan-Meier法结果表明,PSMA5高表达组的患者生存期明显少于低表达组(P<0.001)。敲低PSMA5后,胶质瘤细胞增殖受抑制,诱发细胞周期停滞。结论 PSMA5的高表达水平会导致患者的不良预后,PSMA5可以作为胶质瘤患者预后的预测因素。此外,PSMA5还有作为治疗胶质瘤的生物靶点的潜在作用。Objective To study the expression,function and clinical significance of Proteasome Subunit Alpha Type-5(PSMA5)in glioma.Methods The expression of PSMA5 with the glioma sample information obtained from The Cancer Genome Atlas(TCGA)and Chinese Glioma Genome Atlas(CGGA)were analyzed by using bioinformatics methods.Differentially expressed genes(DEGs)were screened by using the DESeq2 R package,and functional enrichment analysis was performed by using Gene Ontology(GO)and Gene Set Enrichment Analysis(GSEA).Univariate and multivariate Cox regression analysis and Kaplan-Meier method were used to evaluate the impact of PSMA5 on patient prognosis.SiRNA was used to knock down the expression of PSMA5 to explore its effect on the growth of glioma cells.Results PSMA5 was highly expressed in glioma patients(P<0.05),and had a higher expression level in patients with high-grade glioma and isocitrate dehydrogenase 1(IDH1)wild-type glioma(P<0.05).GO and GSEA analysis results showed that PSMA5 was closely related to immune response,mitosis,etc.The results of Cox analysis showed that high expression of PSMA5 was a significant independent prognostic factor for glioma(CGGA:P<0.01,TCGA:P=0.032).The results of the Kaplan-Meier method showed that the survival time of patients in the PSMA5 high expression group was significantly shorter than that in the low expression group(P<0.001).After knocking down PSMA5,glioma cell proliferation was inhibited and cell cycle arrest was induced.Conclusions High expression levels of PSMA5 will lead to poor prognosis in patients.PSMA5 can be used as a predictive factor for the prognosis of glioma patients.In addition,PSMA5 has the potential to serve as a biological target for the treatment of glioma.

关 键 词：蛋白酶体Alpha-5亚单位 神经胶质瘤 基因表达 预后 PSMA5 

分 类 号：R739.41[医药卫生—肿瘤]