基于TCGA数据库口腔鳞状细胞癌相关microRNA预后风险模型的建立

Establishment of Prognostic Risk Model of Oral Squamous Cell Carcinoma Associated microRNA Based on TCGA Database

目的:研究旨在通过检测microRNA(miRNA)的表达特征来预测口腔鳞状细胞癌(OSCC)患者的存活率。方法:从TCGA数据库下载397名OSCC患者的表达谱数据及相应的临床信息。通过生物信息学的方法分析OSCC与正常组织间的差异表达的miRNA,使用Cox回归分析和其他生物信息学方法筛选预后相关的miRNA。并应用采用Kaplan-Meier分析和、受试者工作特征(ROC)曲线分析评估所筛选的miRNA作为预后评估指标的可信度。结果:通过生物信息学的方法分析获得差异表达的miRNA363个,其中上调的miRNA197个,下调的miRNA166个(PDR<0.05)。通过单变量COX回归分析发现84个miRNA的表达与患者预后显著相关,将其中P<0.001的11个miRNA进一步进行多变量COX回归分析,其中4个miRNA(has-mi R-30e、has-mi R-337、has-mi R-6507、has-mi R-1251)纳入了风险评估模型。根据多因素COX分析的回归系数,构建由4个miRNA组成的预后风险评估模型,根据风险评分将OSCC患者分为高风险组和低风险组。Kaplan-Meier生存曲线表明高风险组生存率显著低于低风险组生存率(p=1.026e-05),构建的ROC曲线下面积AUC为0.669,C-index为0.63。结论:4个miRNA,has-mi R-30e、has-mi R-337、has-mi R-6507及has-miR-1251的组合可以作为预测OSCC患者预后的潜在标志物。

Objective:This study aims to predict the survival rate of patients with oral squamous cell carcinoma(OSCC) by detecting the expression of microRNA.Methods:The expression profile data and corresponding clinical information of 397 OSCC patients were downloaded from TCGA database.The differentially expressed miRNAs between OSCC and normal tissues were analyzed by bioinformatics methods,and the prognosis related miRNAs were screened by Cox regression analysis and other bioinformatics methods.Kaplan-Meier analysis and receiver operating characteristic(ROC) curve analysis were used to evaluate the reliability of the selected mi RNAs as prognostic indicators.Results:363 miRNA were differentially expressed by bioinformatics analysis,including 197up-regulated miRNAs and 166 down-regulated miRNAs(FDR<0.05).Through univariate Cox regression analysis,it was found that the expression of 84 miRNAs was significantly correlated with the prognosis of patients.Among them,11 miRNAs with p < 0.001 were further analyzed by multivariable Cox regression analysis,of which 4 miRNAs(has-miR-30e,has-miR-337,has-miR-6507 and has-miR-1251)were included in the risk assessment model.According to the regression coefficient of multivariate COX analysis,a prognostic risk assessment model composed of 4 miRNAs was constructed,and OSCC patients were divided into high risk group and low risk group according to the risk score.Kaplan-Meier survival curve indicates that the survival rate of the high-risk group was significantly lower than that of the low-risk group(p=1.026E-05).The AUC and C-index under the constructed ROC curve were 0.669 and 0.63 respectively.Conclusion:The combination of 4 miRNAs,has-miR-30e,has-miR-337,has-miR-6507 and has-miR-1251,can be used as potential markers to predict the prognosis of OSCC patients.