摘要
目的分析S100钙结合蛋白A11(S100A11)在脑胶质瘤患者中的表达特征及其临床意义。方法回顾性分析中国脑胶质瘤基因组图谱(CGGA)数据库中310例脑胶质瘤患者的临床资料和转录组测序结果。根据患者的病理学特征,评价S100A11在不同分组中的表达特征。同时选用癌症基因组图谱(TCGA)RNA测序数据库中的611例脑胶质瘤患者对其进行验证。采用Kaplan-Meier生存曲线判断S100A11表达量对脑胶质瘤患者生存期的影响。进一步采用单因素和多因素Cox回归分析法评估S100A11表达量是否为影响患者预后的独立危险因素。通过生物信息学分析法获得与S100A11相关基因的生物学功能,以判断S100A11参与脑胶质瘤恶性进展的可能机制。结果在CGGA数据库中,S100A11的表达量随肿瘤世界卫生组织(WHO)分级的升高而增加(Ⅱ、Ⅲ、Ⅳ级依次为:-0.78±0.69、-0.12±0.80、0.62±0.84,F=96.250,P<0.001);S100A11在间质型、异柠檬酸脱氢酶(IDH)野生型和O6-甲基鸟嘌呤-DNA-甲基转移酶(MGMT)启动子非甲基化型脑胶质瘤中的表达水平更高(均P<0.001);在2016年WHO中枢神经系统肿瘤分类中,S100A11在IDH野生型低级别胶质瘤和IDH野生型胶质母细胞瘤中均具有较高的表达(均P<0.001)。S100A11高表达者的总体生存率明显低于低表达者(P<0.05)。S100A11的上述表达特征在TCGA RNA测序数据库中得到相似的结果。多因素Cox回归分析结果显示,S100A11高表达是影响脑胶质瘤患者预后的独立危险因素(HR=1.227,95%CI:0.963~1.538,P=0.014),可用于判断预后。S100A11可能与脑胶质瘤细胞的免疫反应、细胞外基质调控等生物学过程有关。结论S100A11在脑胶质瘤中的表达量与其恶性程度相关,可能通过影响肿瘤细胞的免疫反应参与脑胶质瘤的恶性进展;S100A11可能成为脑胶质瘤患者预后判断的指标及治疗靶点。
Objective To analyze the expression characteristics and clinical significance of S100 calcium binding protein A11(S100A11)in gliomas.Methods Clinical information and sequencing data of 310 glioma samples from Chinese Glioma Genome Atlas(CGGA)database were retrospectively reviewed.The expression characteristics of S100A11 in different groups were analyzed based on pathological feature of the patient.A total of 611 glioma patients from the cancer genome atlas(TCGA)RNA sequencing database were collected to verify the expression patterns of S100A11.Kaplan-Meier survival curve was used to determine the effect of S100A11 expression on the survival of patients with gliomas.Furthermore,univariate and multivariate Cox regression analyses were conducted to determine whether the S100A11 abundance was the independent influencing factor of the outcomes of patients.In addition,the biological functions of S100A11-related genes were obtained by bioinformatics analysis,and possible mechanisms of S100A11 underlying the malignant progression of gliomas were discussed.Results In CGGA database,the expression of S100A11 increased with the increase of WHO pathological grade of glioma(gradeⅡ:-0.78±0.69,gradeⅢ:-0.12±0.80,gradeⅣ:0.62±0.84,F=96.250,P<0.001).Higher expression of S100A11 was found in the mesenchymal subtype,isocitrate dehydrogenase(IDH)wild-type and O6-methylguanine-DNA methyltransferase(MGMT)promoter unmethylated gliomas(all P<0.001).According to the 2016 WHO Classification of Tumors of the Central Nervous System,S100A11 had relatively higher expression in IDH wild-type low-grade glioma and glioblastoma(both P<0.001).Moreover,the cumulative survival rate in S100A11 high-expression group was significantly lower than that in S100A11 low-expression group(P<0.05).The expression characteristics of S100A11 as above were consistent with the results obtained from the TCGA RNA sequencing database.Multivariate analysis showed that S100A11 expression was independent factors for the patient′s outcome(HR=1.227,95%CI:0.963-1.5
作者
曾凡
张莹
赵征
黄华
Zeng Fan;Zhang Ying;Zhao Zheng;Huang Hua(Beijing Neurosurgical Institute,Capital Medical University,Beijing 100070,China)
出处
《中华神经外科杂志》
CSCD
北大核心
2020年第6期622-627,共6页
Chinese Journal of Neurosurgery
基金
国家自然科学基金(81802994)。
