血清MIR4435-2HG在口腔鳞状细胞癌中的预后价值分析

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目的 探讨血清MIR4435-2HG水平在口腔鳞状细胞癌诊断和预后中的价值.方法 本研究为回顾性病例对照研究.纳入癌症和肿瘤基因图谱(the cancer genome atlas project,TCGA)数据库中头颈部鳞状细胞癌的口腔鳞状细胞癌患者518个样本,以长链非编码RNA MIR4435-2HG表达量中位数为界,将患者分为高表达组和低表达组,比较两组患者的5年无病生存率和总生存率.收集2012年1月至2015年1月就诊于湖州师范学院附属口腔医院口腔颌面外科的82例口腔鳞状细胞癌患者的血清标本进行验证,探索MIR4435-2HG的预后价值.通过生物信息学手段预测MIR4435-2HG参与的生物学过程.运用SPSS 23.0设定MIR4435-2HG的最佳诊断和预后截点.结果 分析TCGA数据库中518个口腔鳞状细胞癌患者样本显示,MIR4435-2HG高表达组患者的5年总生存率[43.2%(112/259)]显著低于MIR4435-2HG低表达组[51.7%(134/259)] (P<0.05);MIR4435-2HG高表达组的5年无病生存率[56.8%(147/259)]显著低于MIR4435-2HG低表达组[64.1%(166/259)] (P<0.05).82例口腔鳞状细胞癌患者样本验证结果显示,MIR4435-2HG高表达组的3年总生存率[40.0%(8/20)]显著低于MIR4435-2HG低表达组[80.6% (50/62)] (P<0.05).对血清MIR4435-2HG高表达组和血清MIR4435-2HG低表达组患者的临床病理资料进行比较,结果显示两组患者的性别、年龄、肿瘤发生部位、TNM分期差异均无统计学意义(P>0.05).MIR4435-2HG高表达组的淋巴结转移率[45.0%(9/20)]显著高于低表达组[12.9%(8/62)] (P<0.05),且高表达组的组织学分级[80.0%(16/20)]显著高于低表达组[24.2%(15/62)](x2=20.030,P<0.05).生物信息学分析结果显示,MIR4435-2HG靶基因的生物功能主要富集于蛋白质代谢、核仁和胞质中rRNA的加工、SEMA4D诱导细胞迁移过程、线粒体翻译启动及伸长过程等.结论 血清MIR4435-2HG可作为口腔鳞状细胞癌的潜在预后标志物.“,”Objective To investigate the value of serum MIR4435-2HG level in the diagnosis and prognosis of oral squamous cell carcinoma.Methods This study was a retrospective case-control study.Five hundred and eighteen samples of oral squamous carcinoma of patients with head and neck squamous cell carcinoma in the cancer genome atlas project (TCGA) database,with long noncoding RNA MIR4435-2HG expression.The median was the boundary,and the patients were divided into high expression group and low expression group,and the 5-year disease-free survival rate and overall survival rate of the two groups were compared.Serum samples from 82 patients with oral squamous cell carcinoma who were admitted to the Department of Oral and Maxillofacial Surgery,Affiliated Stomatology Hospital of Huzhou Univerisity from January 2012 to January 2015 were enrolled to verify the prognostic value of MIR4435-2HG.Bioinformatics is used to predict the biological processes involved in MIR4435-2HG.Use the SPSS 23.0 to set the optimal diagnostic and prognostic cutoff for the MIR4435-2HG.Results A total of 518 oral squamous carcinoma patients in the TCGA database showed that the 5-year overall survival rate of the MIR4435-2HG high expression group [43.2% (112/259)] was significanthy lower than that of the MIR4435-2HG low expression group [51.7% (134/259)] (P<0.05).The disease-free survival rate of the MIR4435-2HG high expression group [56.8% (147/259)] was significantly lower than that of the MIR4435-2HG low expression group [64.1% (166/259)] (P<0.05).The results of the validation of 82 patients with oral squamous cell carcinoma suggested that the 3-year overall survival rate of the MIR4435-2HG high expression group [40.0% (8/20)] was significantly lower than the MIR4435-2HG low expression group [80.6 % (50/62)] (P<0.05).The clinical and pathological data of serum MIR4435-2HG high expression group and serum MIR4435-2HG low expression group were compared.The results showed that there was no significant difference in gender,age,tumor location and TNM staging between the two groups (P>0.05).The lymph node metastasis rate of the MIR4435-2HG high expression group was significantly higher than that of the low expression group [12.9% (8/62)] (P<0.05).The histological grade of the high expression group [80.0 % (16/20)] was significantly lower than that of the low expression group [24.2 % (15/62)] (x2=20.030,P<0.05).The results of bioinformatics analysis indicated that the biological functions of MIR4435-2HG target gene were mainly enriched in protein metabolism,processing of rRNA in nucleolus and cytoplasm,SEMA4D induced cell migration process,and mitochondrial translation process.Conclusions Serum MIR4435-2HG can be used as a potential prognostic marker for oral squamous cell carcinoma.
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