脑胶质瘤患者组织和血清外泌体A1BG-AS1的水平及其临床意义

Clinical significances of A1BG-AS1 levels in tissues and serum exosomes of patients with glioma

目的探讨脑胶质瘤患者组织和血清外泌体A1BG反义RNA 1(A1BG-AS1)的水平及其临床意义。方法基于中国脑胶质瘤基因组图谱(CGGA)分析325例脑胶质瘤组织A1BG-AS1水平与临床病理特征和预后的关系。试剂盒提取93例脑胶质瘤患者和86例健康体检者的血清外泌体后采用实时定量PCR(qPCR)检测A1BG-AS1水平,绘制受试者工作特征(ROC)曲线来评估血清外泌体A1BG-AS1对脑胶质瘤的诊断效能,结合脑胶质瘤患者的临床病理特征和随访数据分析血清外泌体A1BG-AS1的临床价值。结果325例脑胶质瘤组织的A1BG-AS1水平为3.053±1.977,且与WHO分级、IDH1突变、1p19q缺失状态和总生存期(OS)有关,其中高水平组的中位OS为523天,短于低水平组的1851天(P<0.05)。93例脑胶质瘤患者的血清外泌体A1BG-AS1的水平为3.820±1.298,高于89例健康体检者的1.759±0.631(P<0.05);ROC曲线结果显示外泌体A1BG-AS1水平诊断脑胶质瘤的曲线下面积为0.894(95%CI:0.841~0.930),且外泌体A1BG-AS1取2.560时约登指数最高(0.724),敏感度和特异度分别为81.72%和90.70%。外泌体A1BG-AS1水平与WHO分级、肿瘤大小、局部浸润、1p19q缺失状态、IDH1突变和OS有关(P<0.05),其中低表达者的中位OS未达,优于高表达者的45.0个月(P<0.05),进一步多因素分析发现外泌体A1BG-AS1水平是OS不良的独立危险因素(HR=2.111,95%CI:1.150~3.872,P=0.044)。结论脑胶质瘤组织和外泌体A1BG-AS1水平升高与脑胶质瘤发生有关,该差异表达基因的临床相关性可作为脑胶质瘤诊断和预后预测的生物标志物并有望成为脑胶质瘤患者的治疗靶点。

Objective To investigate the clinical significance of A1BG antisense RNA 1(A1BG-AS1)levels in tissues and serum exosomes of patients with glioma.Methods Relationship of tissue A1BG-AS1 level with clinicopathological features and prognosis in 325 cases of glioma was analyzed based on Chinese Glioma Genome Atlas(CGGA).After extracting the serum exosomes from 93 patients with glioma and 86 healthy people by kit,A1BG-AS1 level was detected by real-time quantitative PCR(qPCR),and the receiver operating characteristic(ROC)curve was drawn to evaluate the diagnostic efficacy of serum exosomal A1BG-AS1 for glioma.Clinical value of serum exosomal A1BG-AS1 was analyzed according to the clinicopathological features and follow-up data of patients with glioma.Results The level of A1BG-AS1 in 325 gliomas was 3.053±1.977,which was related to WHO grade,IDH1 mutation,1p19q deletion status and overall survival(OS).The median OS in the high-level group was 523 days,shorter than 1851 days in the low-level group(P<0.05).The serum exosomal level of A1BG-AS1 in 93 patients with glioma was 3.820±1.298,which was higher than 1.759±0.631 in 89 healthy subjects(P<0.05).The ROC curve showed that the area under the curve of exosomal A1BG-AS1 level in the diagnosis of glioma was 0.894(95%CI:0.841-0.930),and when exosomal A1BG-AS1 was taken as 2.560,the Jordan index was the highest(0.724)with the sensitivity of 81.72%and specificity of 90.70%.The exosomal level of A1BG-AS1 was related to WHO grade,tumor size,local invasion,1p19q deletion status,IDH1 mutation and OS(P<0.05).The median OS of patients with low expression was unreached,superior to 45.0 months of patients with high expression(P<0.05).Further multivariate analysis showed that the exosomal level of A1BG-AS1 was an independent risk factor for poor OS(HR=2.111,95%CI:1.150-3.872,P=0.044).Conclusion The elevated levels of A1BG-AS1 in glioma tissues and serum exosomes are related to the occurrence of glioma.The clinical correlation of this differentially expressed gene can be used as a biomarker for the diagnosis and prognosis of glioma,and is expected to become a therapeutic target for patients with glioma.