Integrative analysis of genomic and epigenetic regulation of endometrial cancer

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.