Objective: In Sweden, endometrial carcinoma is number five among female cancers, with 1,400 new cases per year. The diagnostic and prognostic markers for the high-risk subgroups with unfavorable prognosis are under intense debate worldwide. The aim of the present study was to address the epigenetic differences in a consecutive series of endometrial carcinomas comprising a low-risk group (FIGO-grade 1) and a high-risk group (FIGO-grade 3) with highly significant different treatment outcomes and survival rates.
Method: We used the Illumina Infinium HumanMethylation450 BeadChip to analyze the DNA methylation pattern and investigated its association with clinicopathological features important for defining the high-risk (FIGO-grade 3) and low-risk (FIGO-grade 1) groups of patients with endometrial cancer.
Results: We identified 2,224 differentially methylated CpG sites. Gene ontology analysis classified the hypomethylated genes in the high-risk group were to cell adhesion and membrane, and the hypomethylated genes to cell adhesion. Increasing methylation level in FIGO-grade 3 cancers was significantly (P < 0.01) associated with advanced tumor stage for CpG sites located in the TBX2, CHST11, LRP5, and CIZ1/ DNM1 genes.
Conclusion: Our study identified specific DNA methylation signature in low-risk and high-risk endometrial tumors, and potential molecular biomarker genes associated with unfavorable clinical predictive and prognostic factors.