A novel epigenetic signature for overall survival prediction in patients with breast cancer.
J Transl Med
; 17(1): 380, 2019 11 20.
Article
en En
| MEDLINE
| ID: mdl-31747912
ABSTRACT
BACKGROUND:
Breast cancer is the most common malignancy in female patients worldwide. Because of its heterogeneity in terms of prognosis and therapeutic response, biomarkers with the potential to predict survival or assist in making treatment decisions in breast cancer patients are essential for an individualised therapy. Epigenetic alterations in the genome of the cancer cells, such as changes in DNA methylation pattern, could be a novel marker with an important role in the initiation and progression of breast cancer.METHOD:
DNA methylation and RNA-seq datasets from The Cancer Genome Atlas (TCGA) were analysed using the Least Absolute Shrinkage and Selection Operator (LASSO) Cox model. Applying gene ontology (GO) and single sample gene set enrichment analysis (ssGSEA) an epigenetic signature associated with the survival of breast cancer patients was constructed that yields the best discrimination between tumour and normal breast tissue. A predictive nomogram was built for the optimal strategy to distinguish between high- and low-risk cases.RESULTS:
The combination of mRNA-expression and of DNA methylation datasets yielded a 13-gene epigenetic signature that identified subset of breast cancer patients with low overall survival. This high-risk group of tumor cases was marked by upregulation of known cancer-related pathways (e.g. mTOR signalling). Subgroup analysis indicated that this epigenetic signature could distinguish high and low-risk patients also in different molecular or histological tumour subtypes (by Her2-, EGFR- or ER expression or different tumour grades). Using Gene Expression Omnibus (GEO) the 13-gene signature was confirmed in four external breast cancer cohorts.CONCLUSION:
An epigenetic signature was discovered that effectively stratifies breast cancer patients into low and high-risk groups. Since its efficiency appears independent of other known classifiers (such as staging, histology, metastasis status, receptor status), it has a high potential to further improve likely individualised therapy in breast cancer.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Regulación Neoplásica de la Expresión Génica
/
Perfilación de la Expresión Génica
/
Epigénesis Genética
Tipo de estudio:
Etiology_studies
/
Incidence_studies
/
Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
J Transl Med
Año:
2019
Tipo del documento:
Article
País de afiliación:
Alemania