DNA甲基化介导的Klotho基因表达沉默在头颈部鳞状细胞癌患者预后研究中的价值

Role of DNA methylation-mediated Klotho gene silencing in the prognosis of head and neck squamous carcinoma

目的研究DNA甲基化介导的Klotho基因表达沉默在头颈部鳞状细胞癌(HNSCC)中的预后价值。方法从癌症基因组图谱(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)V2RSEM值和Klotho基因DNA甲基化的β值的信息,评估Klotho基因表达及其DNA甲基化与患者存活率之间的关系,分析其风险比及其95%置信区间。结果在HNSCC患者中,Klotho基因的表达水平与其DNA甲基化水平相反,且Klotho基因表达水平与HNSCC患者总生存期呈正相关,而其DNA甲基化水平与总生存期呈负相关。此外,Klotho基因DNA甲基化水平与患者的性别肿瘤分级(P<0.01)和肿瘤位置(P<0.01)之间明显相关。结论在HNSCC患者中,Klotho基因DNA甲基化抑制蛋白的表达,Klotho基因低表达及其DNA高甲基化可作为提示患者预后不良的潜在的生物标志。

Objective To study the prognostic value of Klotho gene and its promoter DNA methylation in head and neck squamous cell carcinoma(HNSCC).Methods Upper quartile normalized RNA-seq Upper quartile transcriptome sequencing(V2RSEM)values of Klothogene mRNA and beta value for Klotho gene DNA methylation were retrieved from The Cancer Genome Atlas HNSCC dataset.Kaplan-Meier survival curves were used to assess the associations of Klothogene expression and DNA methylation with survival of patients.The multivariate Cox proportional hazards regression models were used to estimate the hazard ratio and their 95%confidence interval(CI).Results There was a negative relationship between Klotho gene expression and its promoter DNA methylation in HNSCC.Klotho gene expression was positively correlated with overall survival,while Klotho gene methylation was inversely correlated with the overall survival of HNSCC patients.Furthermore,Klotho gene DNA methylation was significantly associated with gender,tumor grade and tumor site(allP<0.01).Conclusion Klotho gene methylation silenced its gene expression in HNSCC.Low Klotho gene expression and high Klotho gene DNA methylation can be potential biomarkers for worse prognosis in HNSCC.