头颈部鳞状细胞癌中Klotho基因表达及其甲基化水平与LC3和NSUN2基因表达的相关性

Klotho Gene Expression and Its Methylation Level are Correlated with LC3 and NSUN2 Gene Expression in Head and Neck Squamous Cell Carcinoma

目的探究头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)中Klotho(KL)基因的表达及其启动子区域甲基化水平与自噬基因LC3和RNA甲基转移酶基因NSUN2之间的关系。方法从癌症基因组图谱(The Cancer Genome Altas,TCGA)数据库中搜集有关HNSCC患者标准化的上四分位转录组测序(RNA-seq V2 RNA-seq by expectation maximization,RSEM)值和KL甲基化的β值(beta-value)信息,采用Kaplan-Meier生存曲线评估KL表达及其启动子区域甲基化与患者存活率之间的关系;采用Spearman相关检测分析KL的表达水平及其启动子区域甲基化水平与LC3和NSUN2表达之间的关系。结果在HNSCC患者当中,KL表达水平与患者的总生存期呈正相关,而KL启动子区域甲基化水平与总生存期间却有着相反的趋势。且KL高水平表达或其启动子区域低水平甲基化的HNSCC患者往往伴有LC3高表达和NSUN2低表达。结论在HNSCC患者中,KL表达水平及其启动子区域甲基化水平可作为提示患者预后的一种潜在的生物标志物,且其下游靶点LC3和NSUN2的表达也会受到KL表达的影响。

Objective To investigate the relationship between Klotho(KL)gene expression and promoter region methylation in head and neck squamous cell carcinoma(HNSCC)and autophagy gene LC3 and RNA methyl transferase gene NSUN2.Methods Information about the standardized upper quartic transcriptional sequencing(RNA-seq)V2 RNA-seq by maximization(RSEM)and the Beta-value of KL methylation was collected from The Cancer Genome Altas(TCGA)database.Kaplan-Meier survival curve was used to evaluate the relationship between KL expression and promoter methylation and patient survival rate.Spearman correlation assay was used to analyze the relationship between KL expression and promoter methylation level and expression levels of LC3 and NSUN2.Results In HNSCC patients,the expression of KL was positively associated with the overall survival,while an inverse trend consisted in the promoter region methylation of KL and the overall survival.HNSCC patients with high KL expression or low promoter region methylation were often accompanied by high LC3 expression and low NSUN2 expression.Conclusion In HNSCC patients,the expression level of KL and the methylation level of its promoter region can be used as a potential biomarker to predict the prognosis of patients,and the expression of its downstream targets LC3 and NSUN2 can also be affected by the expression of KL.