a Department of Otorhinolaryngology Head and Neck Surgery , Lihuili Hospital of Ningbo University , Ningbo , Zhejiang , China.
b Department of Oncology and Hematology , Affiliated Hospital of Medical School of Ningbo University , Ningbo , Zhejiang , China.
Epigenetics. 2018;13(4):398-409. doi: 10.1080/15592294.2018.1465790. Epub 2018 Aug 10.
DNA methylation plays an important role in the etiology and pathogenesis of head and neck squamous cell carcinoma (HNSCC). The current study aimed to identify aberrantly methylated-differentially expressed genes (DEGs) by a comprehensive bioinformatics analysis. In addition, we screened for DEGs affected by DNA methylation modification and further investigated their prognostic values for HNSCC. We included microarray data of DNA methylation (GSE25093 and GSE33202) and gene expression (GSE23036 and GSE58911) from Gene Expression Omnibus. Aberrantly methylated-DEGs were analyzed with R software. The Cancer Genome Atlas (TCGA) RNA sequencing and DNA methylation (Illumina HumanMethylation450) databases were utilized for validation. In total, 27 aberrantly methylated genes accompanied by altered expression were identified. After confirmation by The Cancer Genome Atlas (TCGA) database, 2 hypermethylated-low-expression genes (FAM135B and ZNF610) and 2 hypomethylated-high-expression genes (HOXA9 and DCC) were identified. A receiver operating characteristic (ROC) curve confirmed the diagnostic value of these four methylated genes for HNSCC. Multivariate Cox proportional hazards analysis showed that FAM135B methylation was a favorable independent prognostic biomarker for overall survival of HNSCC patients.
DNA 甲基化在头颈部鳞状细胞癌 (HNSCC) 的病因和发病机制中起着重要作用。本研究旨在通过全面的生物信息学分析来鉴定异常甲基化的差异表达基因 (DEGs)。此外,我们筛选了受 DNA 甲基化修饰影响的 DEGs,并进一步研究了它们对头颈部鳞状细胞癌的预后价值。我们纳入了基因表达综合数据库 (GEO) 中 DNA 甲基化 (GSE25093 和 GSE33202) 和基因表达 (GSE23036 和 GSE58911) 的微阵列数据。使用 R 软件分析异常甲基化的 DEGs。利用癌症基因组图谱 (TCGA) RNA 测序和 DNA 甲基化 (Illumina HumanMethylation450) 数据库进行验证。总共鉴定出 27 个异常甲基化伴表达改变的基因。经过 TCGA 数据库的验证,鉴定出 2 个高甲基化低表达基因 (FAM135B 和 ZNF610) 和 2 个低甲基化高表达基因 (HOXA9 和 DCC)。受试者工作特征 (ROC) 曲线证实了这四个甲基化基因对头颈部鳞状细胞癌的诊断价值。多变量 Cox 比例风险分析表明,FAM135B 甲基化是 HNSCC 患者总生存期的有利独立预后生物标志物。