A network-based approach to identify DNA methylation and its involved molecular pathways in testicular germ cell tumors
A network-based approach to identify DNA methylation and its involved molecular pathways in testicular germ cell tumors
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DOI：
10.7150/jca.27491
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发表时间：
2019-01-01
影响因子：
3.9
通讯作者：
Fan, Liqing
中科院分区：
文献类型：
--
作者：
Bo, Hao;Cao, Ke;Fan, Liqing
背景：睾丸生殖细胞肿瘤（TGCT）是威胁青年男性生殖健康的最常见的睾丸恶性肿瘤。方法：从GEO数据库中收集基因表达谱芯片（GSE 3218、GSE 18155）和基因甲基化芯片（GSE 72444）的数据，通过生物信息学分析，寻找TGCT异常甲基化差异表达的基因和通路。综合分析获得异常甲基化基因。使用大卫数据库进行功能和途径富集分析。蛋白质相互作用（Protein-protein interaction，PPI）网络采用STRING构建，模块分析采用AppMcode。使用GEPIA平台和DiseaseMeth数据库确认hub基因的表达和甲基化水平。结果：共检测到604个低甲基化高表达基因和147个高甲基化低表达基因。高表达的基因在细胞增殖和迁移的生物学过程中富集。PPI网络的前8位枢纽基因为GAPDH、VEGFA、PTPRC、RIPK 4、MMP 9、CSF 1 R、KRAS和FN 1。在GEPIA平台验证后，所有hub基因在TGCT组织中均升高。结论：本研究通过生物信息学分析发现了TGCT中可能存在的甲基化-差异表达基因和通路，为阐明TGCT的发病机制提供了新的思路。
Background: Testicular germ cell tumors (TGCT) is the most common testicular malignancy threaten young male reproductive health. This study aimed to identify aberrantly methylated-differentially expressed genes and pathways in TGCT by comprehensive bioinformatics analysis.Methods: Data of gene expression microarrays (GSE3218, GSE18155) and gene methylation microarrays (GSE72444) were collected from GEO database. Integrated analysis acquired aberrantly methylated-genes. Functional and pathway enrichment analysis were performed using DAVID database. Protein-protein interaction (PPI) network was constructed by STRING and App Mcode was used for module analysis. GEPIA platform and DiseaseMeth database were used for confirming the expression and methylation levels of hub genes. Finally, Human Protein Atlas database was performed to evaluate the prognostic significance.Results: Totally 604 hypomethylation-high expression and 147 hypermethylation-low genes were identified. The high expressed genes were enriched in biological processes of cell proliferation and migration. The top 8 hub genes of PPI network were GAPDH, VEGFA, PTPRC, RIPK4, MMP9, CSF1R, KRAS and FN1. After validation in GEPIA platform, all hub genes were elevated in TGCT tissues. Only MMP9, CSF1R and PTPRC showed hypomethylation-high expression status, which predicted the poor outcome of TGCT patients.Conclusion: Our study indicated possible aberrantly methylated-differentially expressed genes and pathways in TGCT by bioinformatics analysis, which may provide novel insights for unraveling pathogenesis of TGCT.