lncRNA MIR4435-2HG的表达水平及甲基化状态与脑胶质瘤病理分级的关系

Relationship between expression level and methylation status of lncRNA MIR4435-2HG and pathological grade of gliomas

目的探讨长链非编码RNA MIR4435-2HG的表达水平及甲基化状态与脑胶质瘤病理分级的关系。方法选取2019年1~12月手术切除的脑胶质瘤组织110例和颅脑损伤内减压术中切除正常脑组织20例(对照组)。采用实时荧光定量PCR和甲基化特异性PCR检测组织和血清MIR4435-2HG水平及甲基化状态。结果110例胶质瘤中,低级别胶质瘤(WHO分级Ⅰ~Ⅱ级)65例,高级别胶质瘤(WHO分级Ⅲ~Ⅳ级)55例;IDH1突变46例。脑胶质瘤组织和病人血清MIR4435-2HG表达水平均明显高于对照组(P<0.05),而甲基化率明显低于对照组(P<0.05)。低级别胶质瘤组织和病人血清MIR4435-2HG水平明显低于高级别胶质瘤(P<0.05),而甲基化率明显高于高级别胶质瘤(P<0.05)。IDH1突变型胶质瘤组织和病人血清MIR4435-2HG水平明显低于IDH1野生型(P<0.05),而甲基化率明显高于IDH1野生型(P<0.05)。MIR4435-2HG甲基化组胶质瘤组织和血清MIR4435-2HG水平明显低于非甲基化组(P<0.05)。ROC曲线分析显示,血清MIR4435-2HG水平鉴别脑胶质瘤级别的曲线下面积为0.752(95%置信区间0.701~0.804),最佳截断值为1.98,灵敏度和特异度分别为65.0%和91.5%。结论脑胶质瘤,尤其是高级别胶质瘤,血清MIR4435-2HG表达水平普遍升高,检测血清MIR4435-2HG水平有助于鉴别诊断脑胶质瘤级别。MIR4435-2HG转录受其基因甲基化水平的调控,并且与IDH1突变有关。

Objective To investigate the relationship between expression level and methylation status of lncRNA MIR4435-2HG and pathological grade of gliomas.Methods The expression levels and methylation status of lncRNA MIR4435-2HG in glioma tissues and serum obtained from 110 patients(glioma group)with gliomas who underwent microsurgery from January 2019 to December 2019 and in normal cerebral tissues and serum obtained from 20 patients(control group)with traumatic brain injury who underwent decompression were detected by real-time fluorescent quantitative PCR and methylation-specific PCR,respectively.Results Of 110 glioma patients,65 patients were low-grade gliomas(WHO grade Ⅰ~Ⅱ)and 55 were high-grade gliomas(WHO grade Ⅲ~Ⅳ);46 had IDH1 mutations.The expression levels of MIR4435-2HG in glioma tissues and glioma patients'serum were significantly higher than those of the control group(P<0.05),and the methylation rates were significantly lower than those of the control group(P<0.05).The levels of MIR4435-2HG in glioma tissue and serum of low-grade glioma patients were significantly lower than those of high-grade glioma(P<0.05),and the methylation rates were significantly higher than those of high-grade glioma(P<0.05).The levels of MIR4435-2HG in glioma tissue and serum of IDH1 mutant glioma patients were significantly lower than those of IDH1 wild-type glioma(P<0.05),and the methylation rates were significantly higher than those of IDH1 wild-type glioma(P<0.05).The levels of MIR4435-2HG in glioma tissue and serum of the MIR4435-2HG methylated group were significantly lower than those in the non-methylated group(P<0.05).ROC curve analysis showed that the area under curve for serum MIR4435-2HG levels to identify the grade of glioma was 0.752(95%CI 0.701~0.804);the best cutoff value was 1.98;the sensitivity and specificity were 65.0% and 91.5%,respectively.Conclusions The expression level of serum MIR4435-2HG is generally elevated in glioma patients,especially high-grade gliomas.The serum level of MIR4435-2HG is helpful for the differential diagnosis of glioma grades.The transcription of MIR4435-2HG is regulated by its gene methylation level and is related to IDH1 mutation of glioma.