Methylome and transcriptome analyses reveal insights into the epigenetic basis for the good survival of hypomethylated ER-positive breast cancer subtype.
Clin Epigenetics
; 12(1): 16, 2020 01 20.
Article
em En
| MEDLINE
| ID: mdl-31959227
ABSTRACT
BACKGROUND:
Breast cancer (BRCA) is a heterogeneous disease, characterized by different histopathological and clinical features and responses to various therapeutic measures. Despite the research progress of DNA methylation in classification and diagnosis of BRCA and the close relationship between DNA methylation and hormone receptor status, especially estrogen receptor (ER), the epigenetic mechanisms in various BRCA subtypes and the biomarkers associated with diagnostic characteristics of patients under specific hormone receptor status remain elusive.RESULTS:
In this study, we collected and analyzed methylation data from 785 invasive BRCA and 98 normal breast tissue samples from The Cancer Genome Atlas (TCGA) database. Consensus classification analysis revealed that ER-positive BRCA samples were constitutive of two distinct methylation subgroups; with the hypomethylated subgroup showing good survival probability. This finding was further supported by another cohort of ER-positive BRCA containing 30 subjects. Additionally, we identified 977 hypomethylated CpG loci showing significant associations with good survival probability in ER-positive BRCA. Genes with these loci were enriched in cancer-related pathways (e.g., Wnt signaling pathway). Among them, the upregulated 47 genes were also in line with good survival probability of ER-positive BRCA, while they showed significantly negative correlations between their expression and methylation level of certain hypomethylated loci. Functional assay in numerous literatures provided further evidences supporting that some of the loci have close links with the modulation of tumor-suppressive mechanisms via regulation gene transcription (e.g., SFRP1 and WIF1).CONCLUSIONS:
Our study identified a hypomethylated ER-positive BRCA subtype. Notably, this subgroup presented the best survival probability compared with the hypermethylated ER-positive and hypomethylated ER-negative BRCA subtypes. Specifically, we found that certain upregulated genes (e.g., SFRP1 and WIF1) have great potential to suppress the progression of ER-positive BRCA, concurrently exist negative correlations between their expression and methylation of corresponding hypomethylated CpG loci. Therefore, our study indicates that different epigenetic mechanisms likely exist in ER-positive BRCA and provides novel clinical biomarkers specific to ER-positive BRCA diagnosis and therapy.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Receptores de Estrogênio
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Metilação de DNA
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Clin Epigenetics
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China