Abstract
Breast cancer is the most common cancer in the world, and DNA methylation plays a key role in the occurrence and development of breast cancer. However, the effect of DNA methylation in different gene functional regions on gene expression and the effect of gene expression on breast cancer is not completely clear. In our study, we computed and analyzed DNA methylation, gene expression, and clinical data in the TCGA database. Firstly, we calculated the distribution of abnormal DNA methylated probes in 12 regions, found the abnormal DNA methylated probes in down-regulated genes were highly enriched, and the number of hypermethylated probes in the promoter region was 6.5 times than that of hypomethylated probes. Secondly, the correlation coefficients between abnormal DNA methylated values in each functional region of differentially expressed genes and gene expression values were calculated. Then, co-expression analysis of differentially expressed genes was performed, 34 hub genes in cancer-related pathways were obtained, of which 11 genes were regulated by abnormal DNA methylation. Finally, a multivariate Cox regression analysis was performed on 27 probes of 11 genes. Three DNA methylation probes (cg13569051 and cg14399183 of GSN, and cg25274503 of CAV2) related to survival were used to construct a prognostic model, which has a good prognostic ability. Furthermore, we found that the cg25274503 hypermethylation in the promoter region inhibited the expression of the CAV2, and the hypermethylation of cg13569051 and cg14399183 in the 5′UTR region inhibited the expression of GSN. These results may provide possible molecular targets for breast cancer.
Highlights
Breast cancer is the most common malignant tumor in women and the main cause of cancer deaths in women worldwide
We found that the hypermethylated probes in CpG islands (CGI) and promoter regions are highly enriched both before and after normalization
The 27 abnormal DNA methylated probes (ADMPs) that were significantly related to gene expression were obtained
Summary
Breast cancer is the most common malignant tumor in women and the main cause of cancer deaths in women worldwide. DNA methylation is a heritable and reversible epigenetic modification that can regulate gene expression without changing the DNA sequence It mainly occurs at CpG sites and is considered to be a goalkeeper for long-term stable regulation of gene expression (Cedar and Bergman, 2009). DNA methylation of different regions has both positive and negative correlations with gene expression in breast cancer (Győrffy et al, 2016). It has been reported that DNA methylation may play a key role in the process of carcinogenesis by down-regulating the expression of tumor suppressor genes (Jones and Baylin, 2007). The hypermethylation in the promoter region of tumor suppressor genes is related to gene inactivation and transcriptional inhibition, and the hypermethylation of CpG islands (CGI) in the promoter region is considered to be one of the earliest and most frequent changes in cancer (Baylin, 2005; Wittenberger et al, 2014). It is necessary to study the effect of DNA methylation in different regions on gene expression
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