血清lncRNA HOTAIRM1在星型细胞瘤的诊断、预后预测的价值及靶基因预测  

Predictive value of serum lncRNA HOTAIRM1 in the diagnosis and prognosis of astrocytoma and its target gene prediction

作　　者：李斌[1] 李娜[1] 刘家东[1] 李会兵[1] 罗宝昌 LI Bin;LI Na;LIU Jia-dong(Department of Neurosurgery,Hanchuan People＇s Hospital,Hanchuang 431600,China)

机构地区：[1]汉川市人民医院神经外科,汉川431600

出　　处：《临床神经外科杂志》2018年第4期261-266,共6页Journal of Clinical Neurosurgery

摘　　要：目的探讨血清HOTAIRM1在星型细胞瘤诊断和预后预测的价值,以及HOTAIRM1的靶基因和靶基因功能。方法选择2013年1月就诊于汉川市人民医院神经外科的3例星型细胞瘤患者,并与3例健康对照者进行比较。对两组的血清样本进行lncRNA芯片分析,筛选差异表达lncRNA。挑选HOTAIRM1,另取2013年1月至2014年1月就诊于汉川市人民医院神经外科的80例星型细胞瘤患者和25例健康对照者的血清标本用qRT-PCR进行验证。评估HOTAIRM1对星型细胞瘤的诊断效能及其表达水平与预后的关系。运用Multi Experiment Matrix(MEM)在线数据库进行HOTAIRM1的靶基因预测,选取排名前50的靶基因进行GO分析和信号通路分析。结果对3例星型细胞瘤患者和3例健康对照者的血清lncRNA表达谱比较分析,共筛选出338个差异lncRNA,筛选出HOTAIRM1进一步分析。与健康对照者相比,星型细胞瘤患者的血清HOTAIRM1呈低表达(log FC=-1.77,P=0.008)。qRT-PCR验证结果示,星型细胞瘤患者的血清HOTAIRM1表达水平(8.5±0.9)明显低于健康对照者(13.8±3.4)(P=0.000)。ROC曲线分析示血清HOTAIRM1预测星型细胞瘤的曲线下面积为0.730(95%CI:0.624—0.836)。患者的性别、年龄、KPS评分与血清HOTAIRM1的表达水平无明显关系(均P>0.05),较高WHO分级患者的HOTAIRM1表达水平明显低于较低WHO分级患者(P<0.001)。HOTAIRM1低表达组的3年总生存率低于HOTAIRM1高表达组,差异有统计学意义(P=0.006)。生物信息学分析示,HOTAIRM1的靶基因主要富集于微小RNA的生物合成(microRNA biogenesis)和RNA调节(regulatory RNA pathways)等信号通路。结论血清HOTAIRM1可作为星型细胞瘤诊断和预后预测的潜在血清标记物;并有助于为今后进一步临床研究和抗星型细胞瘤治疗靶点设计提供参考。Objective To investigate the predictive value of serum HOTAIRM1 in the diagnosis and prognosis of astrocytoma and to analyze the target gene and target gene function of HOTAIRM1.Methods 3 patients with astrocytoma admitted in our hospital and 3 healthy controls were selected.The lncRNA expression spectrum of serum samples between two groups was compared to screen differentially expressed lncRNA.The lncRNA HOTAIRM1 was selected for further analysis.The serum samples were further collected from 80 cases of astrocytoma patients and 25 healthy controls between January 2013 and January 2014 in our department to confirm the diagnostic value of HOTAIRM1.Finally,the Multi Experiment Matrix（MEM） online database was used to predict the target genes of HOTAIRM1.The top 50 target genes were selected for GO analysis and signal pathway analysis.Results The expression profiles of serum lncRNA in 3 patients with astrocytoma was compared with 3 healthy controls.A total of 338 differentially expressed lncRNA were screened and HOTAIRM1 was selected for further analysis.Compared with healthy controls,HOTAIRM1 showed a lower expression in the serum of patients with astrocytoma（log FC =-1.77,P = 0.008）.Theresults of qRT-PCR showed that the expression level of serum HOTAIRM1 in astrocytoma patients was lower than that in healthy controls（8.5 ± 0.9 vs 13.8 ± 3.4,P = 0.000）.The ROC curve analysis showed that the area under the curve of serum HOTAIRM1 for predicting astrocytoma was 0.730（95% CI：0.624-0.836）.Gender,age,and KPS score were not related to serum HOTAIRM1 levels（all P 〉 0.05） and higher WHO tumor grade was associated with lower HOTAIRM1 expression levels.The 3 year overall survival rate of the HOTAIRM1 low expression group was worse than that of the HOTAIRM1 high expression group（P = 0.006）.Bioinformatics analysis suggested that the target genes of HOTAIRM1 were mainly enriched in the signaling pathways of microRNA biogenesis and RNA regulatory pathways.Conclusion Current study screened serum HOTAI

关 键 词：HOTAIRM1 星型细胞瘤 诊断 预后 靶基因 

分 类 号：R-331[医药卫生]