MeCP2在胶质瘤中的表达水平与患者显微手术预后的关系

Relationship between expression of MeCP2 and prognosis of patients treated by microsurgery in glioma

背景甲基化CpG结合蛋白2(methyl-CpG-binding protein 2,MeCP2)在基因转录调控中发挥重要作用,研究表明MeCP2可能是胶质瘤治疗的一个新靶点,但其在胶质瘤中的表达与患者预后的关系尚不清楚。目的探讨MeCP2在胶质瘤中的表达与患者手术后临床预后的关系。方法选择2016年1月—2018年10月在贵阳市第二人民医院神经外科手术治疗的临床病理资料完整的96例胶质瘤患者,应用免疫组织化学方法检测肿瘤组织和正常脑组织中MeCP2的表达,随访患者生存情况。采用Kaplan-Meier法进行生存分析;采用Cox单因素和多因素风险回归模型分析MeCP2表达水平及相关临床病理因素与患者生存预后的关系。结果96例患者获得随访,其中男51例,女45例,年龄7~79岁,平均年龄(44.9±18.3)岁。免疫组化结果显示胶质瘤组织中MeCP2阳性表达率高于正常脑组织(75.0%vs 30.0%,P<0.05)。MeCP2表达的阳性率在WHOⅠ~Ⅳ级胶质瘤组织中分别为20.0%、66.7%、75.0%、90.6%(1/5、18/27、24/32、29/32),在高级别胶质瘤(WHOⅢ、Ⅳ级)中的阳性表达率高于低级别胶质瘤(WHOⅠ、Ⅱ级),差异有统计学意义(P<0.05)。70例出现肿瘤复发,59例死亡,中位无进展生存期(progression-free survival,PFS)和总生存期(overall survival,OS)分别为(10.7±1.7)个月和(24.1±2.9)个月。Kaplan-Meier生存分析显示,胶质瘤患者中MeCP2高表达组的中位PFS和OS显著低于低表达组[PFS:(15.6±1.8)个月vs(28.0±2.6)个月,P=0.026;OS:(16.1±2.0)个月vs(28.3±5.8)个月,P=0.022]。Cox回归分析显示,MeCP2高表达(HR:1.705,95%CI:1.019~2.854)、肿瘤病变多发(HR:2.727,95%CI:1.453~5.120)、单纯采用手术治疗(HR:1.704,95%CI:1.015~2.861)、高病理级别(WHOⅢ、Ⅳ级)(HR:3.294,95%CI:2.317~4.683)是胶质瘤患者预后不良的独立危险因素。结论MeCP2在胶质瘤手术患者中表达水平上调,且高表达水平与胶质瘤患者术后不良预后相关。

Background Methyl-CpG-binding protein 2(MeCP2)plays an important role in gene transcription regulation.Studies have shown that MeCP2 may be a new therapeutic target in glioma,but the relationship between its expression in glioma and the prognosis of patients is still unclear.Objective To explore the relationship between the expression of MeCP2 and clinical prognosis of patients treated by microsurgery in glioma.Methods A total of 96 glioma patients with complete clinicopathological data who underwent surgical treatment from January 2016 to October 2018 were collected from Department of Neurosurgery,the Second People’s Hospital of Guiyang.The expression level of MeCP2 in tumor tissue and normal tissue were detected by immunohistochemical method and the survival of patients was followed up.The Kaplan-Meier method was used for survival analysis.Univariate and multivariate Cox regression analysis were used to identify the expression level of MeCP2 and related clinicopathological factors with patients survival prognosis.Results All the 96 patients were followed up,including 51 males and 45 females,aged from 7 to 79 years,with an average age of(44.9±18.3)years.Immunohistochemical staining indicated that the positive rate of MeCP2 expression in glioma was significantly higher than those in normal brain tissues(75.0%vs 30.0%,P<0.05).The positive rate of MeCP2 expression in WHOⅠ-Ⅳgrade glioma tissues were 20.0%,66.7%,75.0%,90.6%(1/5,18/27,24/32,29/32),respectively.The positive expression rate of MeCP2 in high-grade gliomas(WHO gradeⅢandⅣ)was significantly higher than that in low-grade gliomas(WHO gradeⅠandⅡ)(P<0.05).Moreover,70 patients had tumor recurrence and 59 patients died.The median PFS and OS were(10.7±1.7)months and(24.1±2.9)months,respectively.Kaplan-Meier survival analysis showed that the median PFS and OS in the high expression group of MeCP2 were significantly lower than those in the low expression group(PFS:[15.6±1.8]months vs[28.0±2.6]months,P=0.026;OS:[16.1±2.0]months vs[28.3±5.8]months,P=0.022).Cox analysis suggested that high expression of MeCP2(HR:1.705,95%CI:1.019-2.854),multiple tumors(HR:2.727,95%CI:1.453-5.120),surgery alone(HR:1.704,95%CI:1.015-2.861)and high pathological grade(WHO gradeⅢ-Ⅳ)(HR:3.294,95%CI:2.317-4.683)were independently associated with poor prognosis of glioma patients.Conclusion MeCP2 is up-regulated in patients undergoing glioma surgery,and the high expression level of MeCP2 is related to the poor prognosis of glioma patients after surgery.