DNA methylation subtypes for ovarian cancer prognosis.

Abstract

Ovarian cancer is one of three major malignancies of the female reproductive system. DNA methylation (MET) is closely related to ovarian cancer occurrence and development, and as such, elucidation of effective MET subtype markers may guide individualized treatment and improve ovarian cancer prognosis. To identify potential markers, we downloaded a total of 571 ovarian cancer MET samples from The Cancer Genome Atlas (TCGA), and established a Cox proportional hazards model using the MET spectrum and clinical pathological parameters. A total of 250 prognosis-related MET loci were obtained by Cox regression, and six molecular subtypes were screened by consensus clustering of CpG loci with a significant difference in both univariate and multivariate analyses. There was a remarkable MET difference between most subtypes. Cluster 2 had the highest MET level and demonstrated the best prognosis, while Clusters 4 and 5 had MET levels significantly lower than those of the other subtypes and demonstrated very poor prognosis. All Cluster 5 samples were at a high grade, while the percentage of stage IV samples in Cluster 4 was greater than in the other subtypes. We obtained five CpG loci using a coexpression network: cg27625732, cg00431050, cg22197830, cg03152385, and cg22809047. Our cluster analysis showed that prognosis in patients with hypomethylation was significantly worse than in patients with hypermethylation. These MET molecular subtypes can be used not only to evaluate ovarian cancer prognosis, but also to fully distinguish the tumor stage and histological grade in patients with ovarian cancer.