Hui Lian, Zhang Jingru, Ding Xiaoxu, Guo Xing, Jang Xuejun
Department of Otolaryngology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
Oncol Lett. 2017 Dec;14(6):7171-7178. doi: 10.3892/ol.2017.7083. Epub 2017 Sep 27.
The present study aimed to identify potentially critical differentially methylated genes associated with the progression of nasopharyngeal carcinoma (NPC). Methylation profiling data of GSE62336 deposited in the Gene Expression Omnibus database were used to identify differentially methylated regions (DMRs) and differentially methylated CpG islands (DMIs). Concurrently, differentially expressed genes (DEGs) were identified using a meta-analysis of three gene expression datasets (GSE53819, GSE13597 and GSE12452). Subsequently, methylated DEGs were identified by comparing DMRs and DEGs. Furthermore, functional associations of these methylated DEGs were analyzed via constructing a functional network using GeneMANIA prediction server. In total, 1,676 hypermethylated genes, 28 hypomethylated genes, 17 DMIs and 2,983 DEGs (1,655 upregulated and 1,328 downregulated) were identified. Among these DEGs, 135 downregulated genes were hypermethylated; of these, dual specificity phosphatase 6 () and tenascin XB () contained DMIs. In the functional network, 154 genes and 1,651 association pairs were included. was predicted to exhibit genetic interactions with other hypermethylated DEGs such as malic enzyme 3 and ST3 β-galactoside α-2,3-sialyltransferase 5; was predicted to be co-expressed with a set of hypermethylated DEGs, including EPH receptor B6, aldehyde dehydrogenase 1 family, member L1 and glutathione peroxidase 3. The hypermethylated DEGs may be involved in the progression of NPC, and they may become novel therapeutic targets for NPC.
本研究旨在鉴定与鼻咽癌(NPC)进展相关的潜在关键差异甲基化基因。利用基因表达综合数据库中存储的GSE62336甲基化谱数据来鉴定差异甲基化区域(DMR)和差异甲基化CpG岛(DMI)。同时,通过对三个基因表达数据集(GSE53819、GSE13597和GSE12452)进行荟萃分析来鉴定差异表达基因(DEG)。随后,通过比较DMR和DEG来鉴定甲基化DEG。此外,使用GeneMANIA预测服务器构建功能网络,分析这些甲基化DEG的功能关联。总共鉴定出1676个高甲基化基因、28个低甲基化基因、17个DMI和2983个DEG(1655个上调和1328个下调)。在这些DEG中,135个下调基因是高甲基化的;其中,双特异性磷酸酶6()和腱生蛋白XB()含有DMI。在功能网络中,包含154个基因和1651个关联对。预测与其他高甲基化DEG如苹果酸酶3和ST3β-半乳糖苷α-2,3-唾液酸转移酶5存在遗传相互作用;预测与一组高甲基化DEG共表达,包括EPH受体B6、醛脱氢酶1家族成员L1和谷胱甘肽过氧化物酶3。高甲基化DEG可能参与NPC的进展,它们可能成为NPC的新型治疗靶点。