Abstract
Endometrial cancer is highly malignant and has a poor prognosis in the advanced stage, thus, prediction of its prognosis is important. DNA methylation has rapidly gained clinical attention as a biomarker for diagnostic, prognostic and predictive purposes in various cancers. In present study, differentially methylated positions and differentially expressed genes were identified according to DNA methylation and RNA-Seq data. Functional analyses and interaction network were performed to identify hub genes, and overall survival analysis of hub genes were validated. The top genes were evaluated by immunohistochemical staining of endometrial cancer tissues. The gene function was evaluated by cell growth curve after knockdown CDC20 and CCNA2 of endometrial cancer cell line. A total of 329 hypomethylated highly expressed genes and 359 hypermethylated lowly expressed genes were identified, and four hub genes were obtained according to the interaction network. Patients with low expression of CDC20 and CCNA2 showed better overall survival. The results also were demonstrated by the immunohistochemical staining. Cell growth curve also demonstrated that knockdown CDC20 and CCNA2 can suppress the cell proliferation. We have identified two aberrantly methylated genes, CDC20 and CCNA2 as novel biomarkers for precision diagnosis in EC.
Highlights
Endometrial cancer (EC) is a gynecological cancer that is commonly diagnosed in developed countries, accounting for approximately 7% of new cancer cases and 4% of cancer-related deaths in women[1]
A few specific DNA methylation signatures associated with high-risk EC and a series of altered methylation genes associated with unfavorable prognostic factors have been identified, such as TBX2, CHST11, PTEN and NID218–20
We mapped the differentially methylated promoter positions (DMPs) to gene promoters, and in cases with multiple DMPs in the same promoter region, we chose the consistently upregulated or downregulated positions as the valid DMP for the differentially methylated gene (DMG)
Summary
Endometrial cancer (EC) is a gynecological cancer that is commonly diagnosed in developed countries, accounting for approximately 7% of new cancer cases and 4% of cancer-related deaths in women[1]. A few specific DNA methylation signatures associated with high-risk EC and a series of altered methylation genes associated with unfavorable prognostic factors have been identified, such as TBX2, CHST11, PTEN and NID218–20. Methylation studies in EC are still preclinical, the understanding of how DNA methylation is associated with the prognosis of EC should continue to develop so that we can accurately predict the prognosis and improve the survival time of EC patients. The present study investigated altered DNA methylation patterns by integrating methylomes and transcriptomes of both EC and normal tissues available in the TCGA data portal with DNA-binding proteins and their binding motifs, aiming to identify specific DNA methylation genes as potential biomarkers for predicting the prognosis of EC patients
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
