Breast milk DNA methylation-based potential prognostic biomarkers of triple-negative breast cancer

The discovery of new biomarkers and experimental treatments is critically needed for triple-negative breast cancer (TNBC) because its prognostic biomarkers and therapeutic targets are unavailable. If abnormal DNA methylation is detected noninvasively, potential biomarkers can be provided for detecting TNBC, thereby o↵ering more effective therapeutic choices to help clinicians. In the GEO database, the obtained information was expression microarray data (GSE۶۵۱۹۴, GSE۳۸۹۵۹) and methylation microarray data (GSE۱۳۳۹۱۸). The Limma package and Shinyepico package of the R program was employed to identify di↵erentially expressed genes (DEGs) and differentially methylated genes (DMGs). The DEGs and DMGs overlapped to obtain methylation-regulated DEGs. These genes were subjected to functional enrichment analyses by g: Profiler. The Protein-Protein Interactions Network (PPI-Net) construction and sorting of hub genes were performed by STRING and Cytoscape, respectively. Finally, the findings were verified according to The Cancer Genome Atlas (TCGA) database by the survival curves of univariate Cox regression and gene expression box plots. The overlapped DEGs and DMGs identified ۸۷ downregulated, hypermethylated genes and ۱۳۲ upregulated, hypomethylated genes. The main enrichment of the detected genes was in the biological cell cycle processes, nuclear division, and the negatively regulated PI۳K Akt signalling pathway. Additionally, the identification of ۲۳ hub genes of the PPI-Net was based on the MCODE instrument. Significant alterations in TCGA, including one hypermethylated, downregulated gene c-KIT and three hypomethylated, upregulated genes BUB۱B, BIRC۵, and CENPE, were observed in the expression and methylation conditions of the four hub genes. Conclusions: Crucial methylation-regulated DEGs were detected in this study, and their associated pathways and biological function were discovered in TBNC. Based on these results, promising prognostic biomarkers may be provided by using breast milk as a biospecimen to evaluate forthcoming diseases.

کلیدواژه ها:

Breast milk ، Methylated gene ، Hub gene ، Biomarkers ، TNBC