DNA methylation biomarkers for nasopharyngeal carcinoma
DNA methylation biomarkers for nasopharyngeal carcinoma
复制标题
DOI：
10.1371/journal.pone.0230524
复制
发表时间：
2020-04-09
期刊：
影响因子：
3.7
通讯作者：
Sun, Haiying
中科院分区：
文献类型：
--
作者：
Han, Baoai;Yang, Xiuping;Sun, Haiying
研究背景DNA甲基化异常在鼻咽癌的发病机制中起重要作用。在本研究中，我们的目的是整合三个队列配置文件数据集，以确定异常甲基化差异表达的基因和通路与NPC.MethodsData的基因表达芯片（GSE 53819，GSE 412452）和基因甲基化芯片（GSE 52068）从GEO数据库中获得。通过GEO 2 R获得异常甲基化的差异表达基因（DEG）。利用大卫数据库对所选基因进行富集和功能分析。为了产生蛋白质-蛋白质相互作用（PPI），使用STRING和Cytoscape软件。结果共筛选出181个低甲基化高表达基因，这些基因在内胚层细胞分化、有丝分裂核分裂、有丝分裂细胞周期、染色体分离和细胞周期转换等生物学机制中富集，富集途径包括ECM-受体相互作用、PI 3 K-Akt信号通路、Focal adhesion、蛋白质消化吸收和阿米巴病等。PPI网络的前3位枢纽基因是FANCI、POR 4和IFIH 1。此外，我们还鉴定了210个高甲基化低表达基因，我们的数据显示，这些基因在轴丝组装、微管形成、轴丝动力蛋白复合物组装、纤毛运动和纤毛组织等生物学过程中富集。通路分析表明，在B细胞受体信号通路、造血细胞谱系、白细胞跨内皮迁移、ZMYND 10、PACRG和POU 2AF 1被确定为PPI网络的前三个枢纽基因。在TCGA和GEPIA数据库中验证后，大多数枢纽基因仍然具有显著性。高表达的POR 4的患者发现有较短的总生存期，而在高表达的ZMYND 10和POU 2AF 1的患者更长的总survival.ConclusionsThe数据揭示了新的异常甲基化差异表达的基因和途径在鼻咽癌的生物信息学分析，可能提供新的见解的分子机制，鼻咽癌的进展。FANCI、POF 4、IFIH 1、ZMYND 10、PACRG和POU 2AF 1等Hub基因可能成为鼻咽癌精确诊断和治疗的新生物标志物。
BackgroundAberrant methylation of DNA plays an important role in the pathogenesis of nasopharyngeal carcinoma (NPC). In the current study, we aimed to integrate three cohorts profile datasets to identify abnormally methylated-differentially expressed genes and pathways associated with NPC.MethodsData of gene expression microarrays (GSE53819, GSE412452) and gene methylation microarrays (GSE52068) obtained from the GEO database. Aberrantly methylated differentially expressed genes (DEGs) were obtained by GEO2R. The David database was utilized to perform enrichment and functional analysis regarding selected genes. To create a protein-protein interaction (PPI), STRING and Cytoscape software were utilized. The MCODE was used for module analysis of the PPI network.ResultsIn total, 181 hypomethylation-high expression genes were identified, which were enriched in the biological mechanisms involved in the differentiation of endodermal cell, mitotic nuclear division, mitotic cell cycle process, chromosome segregation and cell cycle phase transition, etc. Pathway enrichment showed ECM-receptor interaction, PI3K-Akt signaling pathway, Focal adhesion, Protein digestion and absorption and Amoebiasis, etc. The top 3 hub genes of PPI network were FANCI, POSTN, and IFIH1. Additionally, 210 hypermethylation-low expression genes were identified, and our data revealed enrichment in biological processes including axoneme assembly, micro tubular formation, assembly of axonemal dynein complex, cilium movement and cilium organization, etc. Pathway analysis indicated enrichment in B cell receptor signaling pathway, Hematopoietic cell lineage, Leukocyte transendothelial migration, Complement and coagulation cascades and Fc gamma R-mediated phagocytosis, etc. The ZMYND10, PACRG and POU2AF1 were identified as the top three hub genes of PPI network. After validation in TCGA and GEPIA database, most hub genes remained significant. Patients with high expression of POSTN found to have shorter overall survival, while in patients with high expression of ZMYND10 and POU2AF1 longer overall survival was identified.ConclusionsThe data revealed novel aberrantly methylated-differentially expressed genes and pathways in NPC by bioinformatics analysis, potentially providing novel insights for the molecular mechanisms governing NPC progression. Hub genes including FANCI, POSTN, IFIH1, ZMYND10, PACRG and POU2AF1 might serve as novel biomarkers for precision diagnosis and providing medical treatment for patient with NPC.