ArticleBreast cancer research : BCR2026
Tumour-based DNA methylation markers of breast cancer survival: a pooled analysis of 2157 cases.
Article in Breast cancer research : BCR, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundTumour DNA methylation is a potentially valuable marker of breast cancer survival, but previous studies have been limited by relatively small sample sizes. This study aimed to use a large sample size to identify survival-associated DNA methylation markers and develop a methylation-based signature predictive of breast cancer survival.
methodsWe used DNA methylation data from 2,157 breast tumours collected in the Melbourne Collaborative Cohort Study (MCCS) and nine publicly available datasets. An epigenome-wide association study (EWAS) was conducted for five-year overall survival (N = 1,992 cases). Subgroup analyses were carried out by estrogen receptor status. Pathway enrichment analyses were conducted to identify related biological pathways. Elastic net Cox regression was used to develop a signature of survival from DNA methylation data and clinical characteristics, trained on publicly available datasets and tested in the MCCS (N = 425) in addition to the main clinical characteristics. A set of triple-negative tumours (N = 165) with disease-free survival as the outcome was used for additional replication.
resultsWe identified 2,535 CpGs showing an association (P < 1 × 10
conclusionOur findings revealed numerous CpG sites where tumour DNA methylation was associated with breast cancer survival. A substantial improvement in the accuracy of five-year overall survival prediction was achieved by adding a 228-CpG epigenetic score to the main clinicopathological variables. These results suggest that DNA methylation markers may provide additional prognostic information beyond established clinicopathological factors.
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