Cancer stem cell-mediated drug resistance: A comprehensive gene expression profile analysis in breast cancer

Breast cancer is the most frequently diagnosed malignancy in women and a major public health concern. In the current report, differential expression of the breast cancer resistance promoting genes with a focus on breast cancer stem cell related elements as well as the correlation of their mRNAs with various clinicopathologic characteristics, including molecular subtypes, tumor grade/stage, and methylation status, have been investigated using METABRIC and TCGA datasets. To achieve this goal, we downloaded gene expression data of breast cancer patients from TCGA and METABRIC. Then, statistical analyses were used to assess the correlation between the expression levels of stem cell related drug resistant genes and methylation status, tumor grades, various molecular subtypes, and some cancer hallmark gene sets such as immune evasion, metastasis, and angiogenesis. According to the results of this study, a number of stem cell related drug resistant genes are deregulated in breast cancer patients. Furthermore, we observe negative correlations between methylation of resistance genes and mRNA expression. There is a significant difference in the expression of resistance-promoting genes between different molecular subtypes. As mRNA expression and DNA methylation are clearly related, DNA methylation might be a mechanism that regulates these genes in breast cancer cells. As indicated by the differential expression of resistance-promoting genes among various breast cancer molecular subtypes, these genes may function differently in different subtypes of breast cancer. In conclusion, significant deregulation of resistance-promoting factors indicates that these genes may play a significant role in the development of breast cancer.