卵巢癌中基因表达和 DNA 甲基化谱的综合分析。
Integrated analysis of gene expression and DNA methylation profiles in ovarian cancer.
机构信息
Department of Pathology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.
Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, 410078, People's Republic of China.
出版信息
J Ovarian Res. 2020 Mar 19;13(1):30. doi: 10.1186/s13048-020-00632-9.
BACKGROUND
Ovarian cancer is an epithelial malignancy that intrigues people for its poor outcome and lack of efficient treatment, while methylation is an important mechanism that have been recognized in many malignancies. In this study, we attempt to assess abnormally methylated gene markers and pathways in ovarian cancer by integrating three microarray datasets.
METHODS
Three datasets including expression (GSE26712 and GSE66957) and methylation (GSE81224) datasets were accessed. GEO2R platform was used to detect abnormally methylated-differentially expressed genes. Protein-protein interaction (PPI) networks were built and analysed for hypermethylated and hypermethylated differentially expressed genes using Cytoscape software and Mcode app. GEPIA and cBioPortal platforms were used to validate the expression of the hub genes and the correlation between their mRNA expressions and methylation levels. Kaplan Meier-plotter platform were used to assess the prognostic significance of the hub genes.
RESULTS
Six hundred eighty-one hypomethylated-upregulated genes were detected and involved in Rap1 signaling pathway, biosynthesis of amino acids, endocrine resistance, apoptosis, pathways in cancer. The hub genes were TNF, UBC, SRC, ESR1, CDK1, PECAM1, CXCR4, MUC1, IKBKG. Additionally, 337 hypermethylated-downregulated genes were detected and involved in pathways in cancer, focal adhesion, sphingolipid signaling pathway, EGFR tyrosine kinase inhibitor resistance, cellular senescence. The hub genes were BDNF, CDC42, CD44, PPP2R5C, PTEN, UBB, BMP2, FOXO1, KLHL2. TNF, ESR1, MUC1, CD44, PPP2R5C, PTEN, UBB and FOXO1 showed significant negative correlation between their mRNA expressions and methylation levels. TNF, ESR1 and FOXO1 showed prognostic significance.
CONCLUSIONS
Two novel gene networks were found for ovarian cancer. TNF, ESR1, MUC1 and FOXO1 are our candidate genes that might take part in ovarian cancer progression in an epigenetic approach, TNF, ESR1 and FOXO1 may serve as potential markers for ovarian cancer prognosis evaluation.
背景
卵巢癌是一种上皮性恶性肿瘤，其预后不良且缺乏有效治疗方法，令人关注，而甲基化是在许多恶性肿瘤中已被认识到的重要机制。在这项研究中，我们试图通过整合三个微阵列数据集来评估卵巢癌中异常甲基化的基因标记物和途径。
方法
访问了三个数据集，包括表达（GSE26712 和 GSE66957）和甲基化（GSE81224）数据集。使用 GEO2R 平台检测异常甲基化的差异表达基因。使用 Cytoscape 软件和 Mcode 应用程序构建和分析蛋白质-蛋白质相互作用（PPI）网络，用于超甲基化和超甲基化差异表达基因。使用 GEPIA 和 cBioPortal 平台验证枢纽基因的表达以及它们的 mRNA 表达和甲基化水平之间的相关性。使用 Kaplan Meier-plotter 平台评估枢纽基因的预后意义。
结果
检测到 681 个低甲基化的上调基因，这些基因参与了 Rap1 信号通路、氨基酸生物合成、内分泌抵抗、细胞凋亡、癌症途径。枢纽基因包括 TNF、UBC、SRC、ESR1、CDK1、PECAM1、CXCR4、MUC1、IKBKG。此外，检测到 337 个高甲基化的下调基因，这些基因参与了癌症途径、焦点黏附、鞘脂信号通路、表皮生长因子受体酪氨酸激酶抑制剂耐药性、细胞衰老。枢纽基因包括 BDNF、CDC42、CD44、PPP2R5C、PTEN、UBB、BMP2、FOXO1、KLHL2。TNF、ESR1、MUC1、CD44、PPP2R5C、PTEN、UBB 和 FOXO1 的 mRNA 表达与其甲基化水平之间存在显著的负相关。TNF、ESR1 和 FOXO1 具有预后意义。
结论
发现了两个新的卵巢癌基因网络。TNF、ESR1、MUC1 和 FOXO1 是我们的候选基因，它们可能通过表观遗传途径参与卵巢癌的进展，TNF、ESR1 和 FOXO1 可能作为卵巢癌预后评估的潜在标志物。
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