Flow maximization analysis of cell cycle pathway activation status in breast cancer subtypes

In breast cancer, intrinsic subtypes are classified by PAM50 gene set. Among subtypes, there are several different cancer progressions related with aggressiveness, cell proliferation, and so on. Cell cycle is the main biological pathway for regulation of cell proliferation. Although previous studies supported that it is connected with breast cancer prognosis, there are few studies that investigate which part of cell cycle pathway is different among subtypes. In this paper, we explore KEGG cell cycle pathway with TCGA BRCA RNA expression value by a novel flow maximization technique. Our method has two main features: 1) Split pathway into three-parts by graph topology. 2) Apply flow maximization algorithm to each part differently. Based on maximum flow values and ratio values (flow/capacity), our method discriminates breast cancer subtypes according to aggressiveness. We confirm that cell cycle pathway is highly activated in Basal subtype compared with others. Also we find several genes are related with breast cancer progression, which is well supported by previous studies in the literature.