Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Peking University, Beijing 100191, China.
Aging (Albany NY). 2020 May 15;12(10):9260-9274. doi: 10.18632/aging.103202.
Endometrial carcinomas (EC) are characterized by high DNA copy numbers and DNA methylation aberrations. In this study, we sought to comprehensively explore the effect of these two factors on development and progression of EC by analyzing integrated genomic and epigenetic analysis to. We found high DNA copy number and DNA methylation abnormalities in EC, with 6308 copy-number variation genes (CNV-G) and 4376 methylation genes (MET-G). We used these CNV-G and MET-G to subcategorize the samples for prognostic analysis, and identified three molecular subtypes (iC1, iC2, iC3). Moreover, the subtypes exhibited different tumor immune microenvironment characteristics. A further analysis of their molecular characteristics revealed three potential prognostic markers (KIAA1324, nonexpresser of pathogenesis-related genes1 (NPR1) and idiopathic hypogonadotropic hypogonadism (IHH)). Notably, all three markers showed distinct CNV, DNA methylation, and gene expression profiles. Analysis of mutations among the three subtypes revealed that iC2 had fewer mutations than the other subtypes. Conversely, iC2 showed significantly higher CNV levels than other subtypes. This comprehensive analysis of genomic and epigenetic profiles identified three prognostic markers, therefore, provides new insights into the multi-layered pathology of EC. These can be utilized for accurate treatment of EC patients.
子宫内膜癌(EC)的特点是高 DNA 拷贝数和 DNA 甲基化异常。在这项研究中,我们通过分析整合的基因组和表观遗传分析,试图全面探讨这两个因素对 EC 发展和进展的影响。我们发现 EC 中存在高 DNA 拷贝数和 DNA 甲基化异常,有 6308 个拷贝数变异基因(CNV-G)和 4376 个甲基化基因(MET-G)。我们使用这些 CNV-G 和 MET-G 对样本进行预后分析分类,并确定了三种分子亚型(iC1、iC2、iC3)。此外,这些亚型表现出不同的肿瘤免疫微环境特征。进一步分析其分子特征揭示了三个有潜在预后价值的标志物(KIAA1324、发病相关基因 1 无表达物(NPR1)和特发性低促性腺激素性性腺功能减退症(IHH))。值得注意的是,所有这三个标志物都表现出明显的 CNV、DNA 甲基化和基因表达谱。对三种亚型中的突变分析表明,iC2 的突变比其他亚型少。相反,iC2 的 CNV 水平明显高于其他亚型。对基因组和表观遗传谱的全面分析确定了三个预后标志物,因此为 EC 的多层次病理提供了新的见解。这些标志物可以用于 EC 患者的精准治疗。
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