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Pathol Res Pract. 2019 Jan;215(1):137-143. doi: 10.1016/j.prp.2018.11.002. Epub 2018 Nov 11.

Genome-wide characterization of aberrant DNA methylation patterns and the potential clinical implications in patients with endometrial cancer.

Author information

1
Department of Gynecology, The Affiliated Tumor Hospital, Harbin Medical University, 150081 Harbin, China; Department of Gynaecology and Obstetrics, The General Hospital of Daqing Oil Field, 163000 Daqing, China.
2
Department of Gynaecology and Obstetrics, The General Hospital of Daqing Oil Field, 163000 Daqing, China.
3
Department of Gynecology, The Affiliated Tumor Hospital, Harbin Medical University, 150081 Harbin, China. Electronic address: geliu81@163.com.

Abstract

Aberrant DNA methylation has been implicated in the development of the majority of human cancers. However, the association of aberrant DNA methylation with the clinical characteristics of uterine corpus endometrial carcinoma (UCEC) has not been fully explored. We performed an integrative analysis in order to examine the genome-wide DNA methylation profile and the gene expression profile of 432 UCEC samples and 46 normal tissue samples. A total of 793 differentially methylated regions (DMRs) that were associated with 472 protein-coding genes were identified, including 622 hypermethylated DMRs and 171 hypomethylated DMRs. These DMRs were capable of differentiating UCEC from normal tissues with an accuracy of 99.07% using an unsupervised hierarchical clustering method. The genomic analysis suggested that the hypermethylated DMRs were located in CpG island regions nearer to the transcription start site (TSS) compared with the hypomethylated DMRs. Functional analysis for genes associated with DMRs revealed an enrichment of methylated genes that were involved in key cancer-related biological processes and pathways, such as cell adhesion, cell differentiation and the cAMP signaling pathway. Finally, we performed a correlation analysis of the methylation levels of DMRs and patient survival time, and identified 130 DMRs. These molecular markers could classify patients into high-risk and low-risk groups with significantly different overall survival. Taken together, the present study revealed the potential applications of the detection of aberrant DNA methylation as a valuable prognostic marker for UCEC. The current findings may aid the therapeutic exploitation of UCEC treatment strategies and improve our understanding regarding the regulation of methylation in UCEC.

KEYWORDS:

DNA methylation profiles; Endometrial cancer; Methylation markers; Prognosis

PMID:
30449607
DOI:
10.1016/j.prp.2018.11.002
[Indexed for MEDLINE]

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