Low methylation levels of the SFRP1 gene are associated with the basal-like subtype of breast cancer

Abstract

Epigenetic analyses have shown that aberrant DNA methylation signatures are associated with breast cancer molecular subtypes. In this study, we analyzed the methylation status of breast cancer-related genes in relation to the molecular subtypes and investigated whether the basal-like subtype displays distinct methylation profiles. By using pyrosequencing, we analyzed the DNA methylation status of 5 candidate genes in 60 breast cancer samples. We compared the methylation frequency across the molecular subtypes and analyzed the correlation between methylation levels and clinicopathological characteristics. A total of 59 cases displayed aberrant methylation. Amplification during polymerase chain reaction analysis failed in 1 case. The median methylation levels of the secreted frizzled-related protein 1 (SFRP1) gene were significantly lower in the basal-like subtype compared to the luminal A, luminal B and human epidermal growth factor receptor 2 (HER2) subtypes. Cadherin 13 (H-cadherin; CDH13) methylation levels were significantly higher in the HER2 tumors compared to the luminal A and basal-like subtypes. A comparison of the methylation status with clinicopathological characteristics revealed that the expression of bcl-2, progesterone receptor and epidermal growth factor receptor were associated with SFRP1 gene methylation status. Our results indicate that the basal-like subtype is associated with low methylation levels of the SFRP1 gene, suggesting that the methylation levels of specific breast cancer genes may potentially serve as epigenetic biomarkers and prognostic factors.