Department of Stomatolgy, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
Int J Mol Med. 2019 Sep;44(3):787-796. doi: 10.3892/ijmm.2019.4243. Epub 2019 Jun 13.
This study aimed to identify DNA methylation markers in oral squamous cell carcinoma (OSCC) and to construct a prognostic prediction model of OSCC. For this purpose, the methylation data of patients with OSCC downloaded from The Cancer Genome Atlas were considered as a training dataset. The methylation profiles of GSE37745 for OSCC samples were downloaded from Gene Expression Omnibus and considered as validation dataset. Differentially methylated genes (DMGs) were screened from the TCGA training dataset, followed by co‑methylation analysis using weighted correlation network analysis (WGCNA). Subsequently, the methylation and gene expression levels of DMGs involved in key modules were extracted for correlation analysis. Prognosis‑related methylated genes were screened using the univariate Cox regression analysis. Finally, the risk prediction model was constructed and validated through GSE52793. The results revealed that a total of 948 DMGs with CpGs were screened out. Co‑methylation gene analysis obtained 2 (brown and turquoise) modules involving 380 DMGs. Correlation analysis revealed that the methylation levels of 132 genes negatively correlated with the gene expression levels. By combining with the clinical survival prognosis of samples, 5 optimized prognostic genes [centromere protein V (CENPV), Tubby bipartite transcription factor (TUB), synaptotagmin like 2 (SYTL2), occludin (OCLN) and CAS1 domain containing 1 (CASD1)] were selected for constructing a risk prediction model. It was consistent in the training dataset and GSE52793 that low‑risk samples had a better survival prognosis. On the whole, this study indicates that the constructed risk prediction model based on CENPV, SYTL2, OCLN, CASD1, and TUB may have the potential to be used for predicting the survival prognosis of patients with OSCC.
本研究旨在鉴定口腔鳞状细胞癌(OSCC)中的 DNA 甲基化标志物,并构建 OSCC 的预后预测模型。为此,将从癌症基因组图谱(TCGA)下载的 OSCC 患者的甲基化数据作为训练数据集。从基因表达综合数据库(GEO)下载了用于 OSCC 样本的 GSE37745 的甲基化谱,并将其作为验证数据集。从 TCGA 训练数据集中筛选出差异甲基化基因(DMGs),然后使用加权相关网络分析(WGCNA)进行共甲基化分析。随后,提取关键模块中 DMGs 的甲基化和基因表达水平进行相关性分析。使用单因素 Cox 回归分析筛选预后相关的甲基化基因。最后,通过 GSE52793 构建和验证风险预测模型。结果显示,共筛选出 948 个具有 CpG 的 DMGs。共甲基化基因分析得到 2 个(棕色和绿松石色)模块,涉及 380 个 DMGs。相关性分析表明,132 个基因的甲基化水平与基因表达水平呈负相关。通过结合样本的临床生存预后,选择 5 个优化的预后基因[着丝粒蛋白 V(CENPV)、Tubby 二分体转录因子(TUB)、突触融合蛋白样 2(SYTL2)、闭合蛋白(OCLN)和 CAS 域包含蛋白 1(CASD1)]构建风险预测模型。在训练数据集和 GSE52793 中,低风险样本的生存预后均较好。总体而言,本研究表明,基于 CENPV、SYTL2、OCLN、CASD1 和 TUB 构建的风险预测模型可能有潜力用于预测 OSCC 患者的生存预后。