瘤周水肿区膜联蛋白A2与胶质母细胞瘤患者预后的相关性研究  

Study on the correlation between annexin A2 in the peritumoral brain edema region and prognosis of glioblastoma

作　　者：马凯明 杨军 陈晓东[1] 马路路 马长城[1] 陈新 陈素华 Ma Kaiming;Yang Jun;Chen Xiaodong;Ma Lulu;Ma Changcheng;Chen Xin;Chen Suhua(Department of Neurosurgery,Peking University Third Hospital,Beijing 100191,China;Center for Precision Neurosurgery and Oncology of Peking University Health Science Center,Beijing 100191,China;Department of Endocrinology and Metabolic Disease,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]北京大学第三医院神经外科,北京100191 [2]北京大学医学部精准神经外科与肿瘤研究中心,北京100191 [3]郑州大学第一附属医院内分泌与代谢病科,郑州450052

出　　处：《中华神经外科杂志》2025年第3期227-232,共6页Chinese Journal of Neurosurgery

基　　金：国家自然科学基金(82272675,82072774)。

摘　　要：目的探讨胶质母细胞瘤(GBM)瘤周水肿(PTBE)区膜联蛋白A2(ANXA2)与患者预后的相关性。方法纳入94例2018年6月至2022年10月于北京大学第三医院神经外科行肿瘤切除术的初发小脑幕上GBM患者进行回顾性队列研究。留取PTBE区脑组织,采用实时荧光定量PCR(qRT-PCR)法检测ANXA2基因的表达量,采用蛋白质免疫印迹(WB)法检测ANXA2蛋白的表达量,根据基因或蛋白表达量的中位数将患者分为高表达组和低表达组,每组47例。通过Kaplan-Meier法分析PTBE区ANXA2高、低表达组患者总生存期的差异;采用多因素Cox回归分析法评估PTBE区ANXA2表达水平与患者总生存期的相关性。结果qRT-PCR检测显示,PTBE区ANXA2基因的中位表达量为13.48(0.36~121.37);WB法检测ANXA2蛋白的中位表达量为0.68(0.07~8.53)。94例患者的中位随访时长为21(1~49)个月,随访期共死亡32例。Kaplan-Meier生存分析显示,PTBE区ANXA2基因及蛋白低表达组患者的中位总生存期为20(3~46)个月,高表达组为10(1~29)个月;log-rank检验显示,ANXA2基因或蛋白高表达组与低表达组患者总生存期的差异均有统计学意义(均P<0.01)。多因素Cox回归分析结果显示,1p/19q染色体非共缺失型、O^(6)-甲基鸟嘌呤-DNA甲基转移酶启动子非甲基化型、年龄增大,以及PTBE区ANXA2基因(HR=1.833,95%CI:1.040~3.231)或蛋白(HR=2.043,95%CI:1.158~3.604)高表达均为影响GBM患者总生存期的独立危险因素(均P<0.05)。结论PTBE区ANXA2高表达与GBM患者不良预后相关。ObjectiveTo explore the relationship between the expression of annexin A2(ANXA2)in peritumoral brain edema(PTBE)region and prognosis of glioblastoma.MethodsA retrospective cohort study was conducted on 94 patients with primary supratentorial GBM who underwent tumor resection in the Department of Neurosurgery,Peking University Third Hospital from June 2018 to October 2022.After the brain tissue of PTBE region was retained,the expression of ANXA2 gene was detected by quantitative real-time PCR(qRT-PCR)and the expression of ANXA2 protein was detected by Western Blot(WB).According to the median of gene or protein expression,the patients were divided into high expression group and low expression group,with 47 cases in each group.Kaplan-Meier method was used to analyze the difference in survival time between patients with high and low expression of ANXA2 in PTBE region.Multivariate Cox regression analysis was used to evaluate the correlation between the expression level of ANXA2 in PTBE and the overall survival of patients.ResultsThe results of qRT-PCR showed that the median expression of ANXA2 gene in PTBE region was 13.48(0.36-121.37).The median expression of ANXA2 protein detected by WB was 0.68(0.07-8.53).The median follow-up time of 94 patients was 21(1-49)months,and 32 patients died.Kaplan-Meier survival analysis showed that the median overall survival of patients with low expression of ANXA2 gene and protein in the PTBE region was 20(3-46)months,while the high expression group had a median survival of 10(1-29)months.Log-rank test showed that there were significant differences in survival time between ANXA2 gene or protein high expression group and low expression group(all P<0.01).Multivariate Cox regression analysis showed that the high expression of ANXA2 gene(HR=1.833,95%CI:1.040-3.231)and that of protein(HR=2.043,95%CI:1.158-3.604)in PTBE region,rather than 1p/19q non-codeletion type,O^(6)-methylguanine-DNA methyltransferase promoter non-methylation type and increasing age,were independent risk factors affect

关 键 词：胶质母细胞瘤 预后 膜联蛋白A2 瘤周水肿区 

分 类 号：R739.41[医药卫生—肿瘤]