Signaling Pathway Activities Improve Prognosis for Breast Cancer

Abstract

With the advent of high-throughput technologies for genome-wide expression profiling, a large number of methods have been proposed to discover gene-based signatures as biomarkers to guide cancer prognosis. However, it is often difficult to interpret the list of genes in a prognostic signature regarding the underlying biological processes responsible for disease progression or therapeutic response. A particularly interesting alternative to gene-based biomarkers is mechanistic biomarkers, derived from signaling pathway activities, which are known to play a key role in cancer progression and thus provide more informative insights into cellular functions involved in cancer mechanism. In this study, we demonstrate that pathway-level features, such as the activity of signaling circuits, outperform conventional gene-level features in prediction performance in breast cancer prognosis. We also show that the proposed classification scheme can even suggest, in addition to relevant signaling circuits related to disease outcome, a list of genes that do not code for signaling proteins whose contribution to cancer prognosis potentially supplements the mechanisms detected by pathway analysis.