Research Paper Volume 12, Issue 10 pp 9260—9274
Integrative analysis of genomic and epigenetic regulation of endometrial cancer
- 1 Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
- 2 Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing 100191, China
- 3 Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, China
- 4 Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Peking University, Beijing 100191, China
- 5 Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China
- 6 Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China
- 7 Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China
Received: December 6, 2019 Accepted: April 17, 2020 Published: May 15, 2020
https://doi.org/10.18632/aging.103202How to Cite
Copyright © 2020 Zhong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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.