Lv Liting, Cao Liyu, Hu Guinv, Shen Qinyan, Wu Jinzhong
Department of Thyroid and Breast Surgery, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, China.
Front Genet. 2020 Mar 31;11:294. doi: 10.3389/fgene.2020.00294. eCollection 2020.
Aberrant DNA methylation plays an crucial role in tumorigenesis through regulating gene expression. Nevertheless, the exact role of methylation in the carcinogenesis of thyroid cancer and its association with prognosis remains unclear. The purpose of this study is to explore the DNA methylation-driven genes in thyroid cancer by integrative bioinformatics analysis.
The transcriptome profiling data and DNA methylation data of thyroid cancer were downloaded from The Cancer Genome Atlas (TCGA) database. The methylmix R package was used to screen DNA methylation-driven genes in thyroid cancer. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted to annotate the function of methylation-driven genes. Univariate Cox regression analyses was performed to distinguish prognosis-related methylation-driven genes. Multivariate Cox regression analyses was utilized to build a prognostic multi-gene signature. A survival analysis was carried out to determine the individual prognostic significance of this multi-gene signature.
A total of 51 methylation-driven genes were identified. The functional analysis indicated that these genes were significantly enriched in diverse biological processes (BP) and pathways related to the malignancy processes. Four of these genes (RDH5, TREM1, BIRC7, and SLC26A7) were selected to construct the risk evaluation model. Patients in the low-risk group had an conspicuously better overall survival (OS) than those in high-risk group ( < 0.001). The area under the receiver operating characteristic (ROC) curve for this model was 0.836, suggesting a good specificity and sensitivity. Subsequent survival analysis revealed that this four-gene signature served as an independent indicator for the prognosis of thyroid cancer. Moreover, the prognostic signature was well validated in a external thyroid cancer cohort.
We identified methylation-driven genes in thyroid cancer with independent prognostic value, which may offer new insight into molecular mechanisms of thyroid cancer and provide new possibility for individualized treatment of thyroid cancer patients.
异常的DNA甲基化通过调节基因表达在肿瘤发生中起关键作用。然而，甲基化在甲状腺癌发生中的具体作用及其与预后的关系仍不清楚。本研究的目的是通过综合生物信息学分析探索甲状腺癌中DNA甲基化驱动的基因。
从癌症基因组图谱（TCGA）数据库下载甲状腺癌的转录组谱数据和DNA甲基化数据。使用methylmix R包筛选甲状腺癌中DNA甲基化驱动的基因。进行基因本体（GO）和京都基因与基因组百科全书（KEGG）分析以注释甲基化驱动基因的功能。进行单变量Cox回归分析以区分与预后相关的甲基化驱动基因。利用多变量Cox回归分析构建预后多基因特征。进行生存分析以确定该多基因特征的个体预后意义。
共鉴定出51个甲基化驱动基因。功能分析表明，这些基因在与恶性过程相关的多种生物过程（BP）和途径中显著富集。选择其中四个基因（RDH5、TREM1、BIRC7和SLC26A7）构建风险评估模型。低风险组患者的总生存期（OS）明显优于高风险组患者（<0.001）。该模型的受试者工作特征（ROC）曲线下面积为0.836，表明具有良好的特异性和敏感性。随后的生存分析表明，这个四基因特征可作为甲状腺癌预后的独立指标。此外，该预后特征在一个外部甲状腺癌队列中得到了很好的验证。
我们鉴定出了具有独立预后价值的甲状腺癌甲基化驱动基因，这可能为甲状腺癌的分子机制提供新的见解，并为甲状腺癌患者的个体化治疗提供新的可能性。
