Optimal DNA methylation biomarkers for characterizing triple negative breast cancer

This thesis project is motivated by the urgent needs of biomarkers for characterizing the triple negative breast cancer in clinical practice. DNA methylation plays an important role in cancer development. DNA methylation biomarkers, which use specific methylation changes, provide a range of opportunities for diagnosis, prognosis, and outcome of treatment monitoring. The aim of this study is to identifying the optimal DNA methylation biomarkers for characterizing triple negative breast cancer with minimum cost and accuracy when compared with available methods currently routine used in clinical practice. We performed a series of statistical methods, including paired t test, Bonferroni corrections, cluster analysis, and the combination of structure trimming and top-ranked p values on the DNA methylation data of level three of 46 paired patient samples of breast cancer patient samples from The Cancer Genome Atlas (TCGA). We successfully identified a set of the optimal DNA methylation biomarkers consisting about 56 genes for characterizing triple negative breast cancer samples. Up to date, this set of biomarker is the first set of DNA methylation biomarkers for characterizing triple negative breast cancer samples. The result shows the 14 biomarkers are able to effectively distinguish the triple negative breast cancer samples from other two subtypes of breast cancer samples. Therefore, we can use this optimal set as candidates for future diagnosis, prognosis and monitoring outcomes of treatment in triple negative breast cancer. However, definitely in nearly future, there is a need to use a large clinical trial to further validate the set of biomarkers before it is used really to clinical practice. In addition, we developed the method of combining structure trimming and top-ranked p values to identify optimal DNA methylation biomarkers. In future studies, we can use the method on other types of cancers to identify the optimal DNA methylation biomarkers. Moreover, we found the new DNA methylation biomarkers compared with other similar studies in our set. In subsequent study, we will investigate the role of DNA methylation change of those new genes in triple negative breast cancer